muscarinic agonists

Summary

Summary: Drugs that bind to and activate muscarinic cholinergic receptors (RECEPTORS, MUSCARINIC). Muscarinic agonists are most commonly used when it is desirable to increase smooth muscle tone, especially in the GI tract, urinary bladder and the eye. They may also be used to reduce heart rate.

Top Publications

  1. ncbi Recovery from muscarinic modulation of M current channels requires phosphatidylinositol 4,5-bisphosphate synthesis
    Byung Chang Suh
    Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, WA 98195, USA
    Neuron 35:507-20. 2002
  2. ncbi Relationship between membrane phosphatidylinositol-4,5-bisphosphate and receptor-mediated inhibition of native neuronal M channels
    Joanna S Winks
    1Ion Channel Pharmacology Group, IPC 388, Pfizer Global Research and Development, Sandwich Laboratories, Sandwich, Kent CT13 9NJ, United Kingdom
    J Neurosci 25:3400-13. 2005
  3. ncbi Two distinct classes of muscarinic action on hippocampal inhibitory synapses: M2-mediated direct suppression and M1/M3-mediated indirect suppression through endocannabinoid signalling
    Yuko Fukudome
    Department of Cellular Neurophysiology, Graduate School of Medical Science, Kanazawa University, 13 1 Takara machi, Kanazawa 920 8640, Japan
    Eur J Neurosci 19:2682-92. 2004
  4. ncbi Cholinergic activation of phasic activity in the isolated bladder: possible evidence for M3- and M2-dependent components of a motor/sensory system
    Steven M Finney
    Western General Hospital, Edinburgh, Scotland, UK
    BJU Int 100:668-78. 2007
  5. pmc Inhibition of the mammalian target of rapamycin signaling pathway suppresses dentate granule cell axon sprouting in a rodent model of temporal lobe epilepsy
    Paul S Buckmaster
    Department of Comparative Medicine, Stanford University, Stanford, California 94305, USA
    J Neurosci 29:8259-69. 2009
  6. ncbi Postsynaptic M1 and M3 receptors are responsible for the muscarinic enhancement of retrograde endocannabinoid signalling in the hippocampus
    Takako Ohno-Shosaku
    Department of Cellular Neurophysiology, Graduate School of Medical Science, Kanazawa University, 13 1 Takara machi, Kanazawa 920 8640, Japan
    Eur J Neurosci 18:109-16. 2003
  7. pmc AKAP150 signaling complex promotes suppression of the M-current by muscarinic agonists
    Naoto Hoshi
    Department of Biophysical Genetics, Kanazawa University Graduate School of Medicine, 13 1 Takara machi, Kanazawa, Ishikawa 920 8640, Japan
    Nat Neurosci 6:564-71. 2003
  8. ncbi Evaluating potential therapies for bladder dysfunction in a mouse model of multiple sclerosis with high-resolution ultrasonography
    S Al-Izki
    Neuroscience Centre, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
    Mult Scler 15:795-801. 2009
  9. ncbi Inhibitory actions of calcitonin gene-related peptide and capsaicin: evidence for local axonal reflexes in the bladder wall
    James I Gillespie
    The Urophysiology Research Group, School of Surgical and Reproductive Sciences, The Medical School, The University, Newcastle upon Tyne NE2 4HH, UK
    BJU Int 95:149-56. 2005
  10. ncbi Nuclear calcium signaling evoked by cholinergic stimulation in hippocampal CA1 pyramidal neurons
    John M Power
    Division of Neuroscience, John Curtin School for Medical Research, Australian National University, Canberra, ACT 0200, Australia
    J Neurosci 22:3454-62. 2002

Detail Information

Publications297 found, 100 shown here

  1. ncbi Recovery from muscarinic modulation of M current channels requires phosphatidylinositol 4,5-bisphosphate synthesis
    Byung Chang Suh
    Department of Physiology and Biophysics, University of Washington School of Medicine, Seattle, WA 98195, USA
    Neuron 35:507-20. 2002
    ..Lipid phosphorylation by PI 4-kinase is required for recovery from muscarinic modulation of M current...
  2. ncbi Relationship between membrane phosphatidylinositol-4,5-bisphosphate and receptor-mediated inhibition of native neuronal M channels
    Joanna S Winks
    1Ion Channel Pharmacology Group, IPC 388, Pfizer Global Research and Development, Sandwich Laboratories, Sandwich, Kent CT13 9NJ, United Kingdom
    J Neurosci 25:3400-13. 2005
    ....
  3. ncbi Two distinct classes of muscarinic action on hippocampal inhibitory synapses: M2-mediated direct suppression and M1/M3-mediated indirect suppression through endocannabinoid signalling
    Yuko Fukudome
    Department of Cellular Neurophysiology, Graduate School of Medical Science, Kanazawa University, 13 1 Takara machi, Kanazawa 920 8640, Japan
    Eur J Neurosci 19:2682-92. 2004
    ..Thus, the muscarinic system can influence hippocampal functions by controlling different subsets of inhibitory synapses through the two distinct mechanisms...
  4. ncbi Cholinergic activation of phasic activity in the isolated bladder: possible evidence for M3- and M2-dependent components of a motor/sensory system
    Steven M Finney
    Western General Hospital, Edinburgh, Scotland, UK
    BJU Int 100:668-78. 2007
    To analyse pressure changes induced by muscarinic agonists on the isolated bladder in order to examine whether there are different responses representing different components of a motor/sensory system within the bladder wall.
  5. pmc Inhibition of the mammalian target of rapamycin signaling pathway suppresses dentate granule cell axon sprouting in a rodent model of temporal lobe epilepsy
    Paul S Buckmaster
    Department of Comparative Medicine, Stanford University, Stanford, California 94305, USA
    J Neurosci 29:8259-69. 2009
    ..However, suppression required continual treatment, and rapamycin treatment did not reverse already established axon reorganization...
  6. ncbi Postsynaptic M1 and M3 receptors are responsible for the muscarinic enhancement of retrograde endocannabinoid signalling in the hippocampus
    Takako Ohno-Shosaku
    Department of Cellular Neurophysiology, Graduate School of Medical Science, Kanazawa University, 13 1 Takara machi, Kanazawa 920 8640, Japan
    Eur J Neurosci 18:109-16. 2003
    ..These results indicate that the activation of postsynaptic M1 and M3 receptors facilitates the depolarization-induced release of endocannabinoids...
  7. pmc AKAP150 signaling complex promotes suppression of the M-current by muscarinic agonists
    Naoto Hoshi
    Department of Biophysical Genetics, Kanazawa University Graduate School of Medicine, 13 1 Takara machi, Kanazawa, Ishikawa 920 8640, Japan
    Nat Neurosci 6:564-71. 2003
    ..These inhibitors also reduced muscarinic inhibition of M-current. Our data indicate that AKAP150-bound PKC participates in receptor-induced inhibition of the M-current...
  8. ncbi Evaluating potential therapies for bladder dysfunction in a mouse model of multiple sclerosis with high-resolution ultrasonography
    S Al-Izki
    Neuroscience Centre, Barts and the London School of Medicine and Dentistry, Queen Mary University of London, London, UK
    Mult Scler 15:795-801. 2009
    ..Such signs can develop in animal models of MS. Current assessments of bladder properties in animal models are generally invasive, electrophysiological techniques...
  9. ncbi Inhibitory actions of calcitonin gene-related peptide and capsaicin: evidence for local axonal reflexes in the bladder wall
    James I Gillespie
    The Urophysiology Research Group, School of Surgical and Reproductive Sciences, The Medical School, The University, Newcastle upon Tyne NE2 4HH, UK
    BJU Int 95:149-56. 2005
    ....
  10. ncbi Nuclear calcium signaling evoked by cholinergic stimulation in hippocampal CA1 pyramidal neurons
    John M Power
    Division of Neuroscience, John Curtin School for Medical Research, Australian National University, Canberra, ACT 0200, Australia
    J Neurosci 22:3454-62. 2002
    ..Because rises in nuclear calcium are known to initiate the transcription of novel genes, we suggest that these actions of cholinergic stimulation may underlie its effects on learning and memory...
  11. ncbi M1 muscarinic agonists as potential disease-modifying agents in Alzheimer's disease. Rationale and perspectives
    A Fisher
    Israel Institute for Biological Research, P O Box 19, Ness Ziona 74100, Israel
    Ann N Y Acad Sci 920:315-20. 2000
    ..This unique property of M1 agonists to alter different aspects of AD pathogenesis could represent the most remarkable, yet unexplored, clinical value of such compounds...
  12. ncbi Importance and prospects for design of selective muscarinic agonists
    J Jakubik
    Department of Neurochemistry, Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic
    Physiol Res 57:S39-47. 2008
    ..The selectivity of classical muscarinic agonists among receptor subtypes is very low due to the highly conserved nature of the orthosteric binding site ..
  13. ncbi Therapeutic strategies in Alzheimer's disease: M1 muscarinic agonists
    A Fisher
    Israel Institute for Biological Research, Ness Ziona
    Jpn J Pharmacol 84:101-12. 2000
    ..The therapeutic potential of M1-selective muscarinic agonists including AF102B, AF150(S), AF267B (the AF series) is evaluated and compared, when possible, with several ..
  14. ncbi Enhanced proliferation of acinar and progenitor cells by prophylactic pilocarpine treatment underlies the observed amelioration of radiation injury to parotid glands
    Fred R Burlage
    Department of Radiation Oncology, University Medical Center Groningen, The Netherlands
    Radiother Oncol 90:253-6. 2009
    ..In this study, this hypothesis is tested directly, by assessing the proliferation of progenitor and secretory cells in irradiated and non-irradiated parotid gland tissue...
  15. pmc Muscarinic receptor agonists stimulate human colon cancer cell migration and invasion
    Angelica Belo
    Division of Gastroenterology and Hepatology, Univ of Maryland School of Medicine, Baltimore, 21201, USA
    Am J Physiol Gastrointest Liver Physiol 300:G749-60. 2011
    ..In concert with previous observations, these findings indicate that muscarinic receptor signaling plays a key role in colon cancer cell proliferation, survival, migration, and invasion...
  16. pmc Cholinergic dilation of cerebral blood vessels is abolished in M(5) muscarinic acetylcholine receptor knockout mice
    M Yamada
    Laboratory of Bioorganic Chemistry National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 98:14096-101. 2001
    ....
  17. pmc Muscarinic receptor agonists stimulate matrix metalloproteinase 1-dependent invasion of human colon cancer cells
    Jean Pierre Raufman
    Division of Gastroenterology and Hepatology, University of Maryland School of Medicine, Baltimore, MD 21201, USA
    Biochem Biophys Res Commun 415:319-24. 2011
    ....
  18. ncbi Muscarinic agonists activate Ca2+ store-operated and -independent ionic currents in insulin-secreting HIT-T15 cells and mouse pancreatic beta-cells
    D Mears
    Department of Anatomy, Physiology and Genetics, Uniformed Services University of the Health Sciences, Bethesda, MD 20814, USA
    J Membr Biol 197:59-70. 2004
    ..We conclude that I(musc) consists of store-operated and store-independent components, both of which may contribute to the depolarizing action of muscarinic agonists on pancreatic beta-cells.
  19. ncbi Cholinergic treatments with emphasis on m1 muscarinic agonists as potential disease-modifying agents for Alzheimer's disease
    Abraham Fisher
    Israel Institute for Biological Research, PO Box 19, Ness Ziona, Israel
    Neurotherapeutics 5:433-42. 2008
    ..the advantages and drawbacks of some cholinergic compounds, such as acetylcholinesterase inhibitors, M1 muscarinic agonists, M2 antagonists, and nicotinic agonists...
  20. ncbi Muscarine reduces calcium-dependent electrical activity in substantia nigra dopaminergic neurons
    R S Scroggs
    Department of Anatomy and Neurobiology, Health Science Center, University of Tennessee, Memphis, Tennessee 38163, USA
    J Neurophysiol 86:2966-72. 2001
    ....
  21. ncbi New insights from the use of pilocarpine and kainate models
    J P Leite
    Department of Neurology, University of São Paulo School of Medicine at Ribeirão Preto, Campus Universitario, Ribeirao Preto, Brazil
    Epilepsy Res 50:93-103. 2002
    ..Most of current tools used to quantify spontaneous seizure events need to be coupled to electrophysiology and more sophisticated systems for recording and analyzing behavior...
  22. pmc Facilitation of long-term potentiation by muscarinic M(1) receptors is mediated by inhibition of SK channels
    Katherine A Buchanan
    Medical Research Council Centre for Synaptic Plasticity, School of Physiology and Pharmacology, University of Bristol, University Walk, Bristol BS8 1TD, UK
    Neuron 68:948-63. 2010
    ..Thus, we describe a mechanism where M(1) receptor activation inhibits SK channels, allowing enhanced NMDAR activity and leading to a facilitation of LTP induction in the hippocampus...
  23. pmc Origin of spontaneous activity in neonatal and adult rat bladders and its enhancement by stretch and muscarinic agonists
    A Kanai
    Department of Medicine, University of Pittsburgh School of Medicine, A1224 Scaife Hall, Pittsburgh, PA 15261, USA
    Am J Physiol Renal Physiol 292:F1065-72. 2007
    ..the origin of spontaneous activity in neonatal and adult rat bladders and the effect of stretch and muscarinic agonists and antagonists on spontaneous activity...
  24. ncbi A muscarinic cholinergic mechanism underlies activation of the central pattern generator for locust flight
    Edgar Buhl
    University of Leipzig, Institute of Biology II, Talstr 33, 04103 Leipzig, Germany
    J Exp Biol 211:2346-57. 2008
    ....
  25. pmc Acute induction of epileptiform discharges by pilocarpine in the in vitro isolated guinea-pig brain requires enhancement of blood-brain barrier permeability
    L Uva
    Unit of Experimental Neurophysiology and Epileptology, Fondazione Istituto Neurologico, Via Celoria 11, 20133 Milan, Italy
    Neuroscience 151:303-12. 2008
    ..Pilocarpine accumulation secondary to BBB permeability changes may contribute to in vivo ictogenesis in the pilocarpine epilepsy model...
  26. pmc Temporal characterization of changes in hippocampal cannabinoid CB(1) receptor expression following pilocarpine-induced status epilepticus
    Katherine W Falenski
    Department of Neurology, Virginia Commonwealth University, PO Box 980599, Richmond, VA 23298, USA
    Brain Res 1262:64-72. 2009
    ..This suggests a role for dysregulation of the endocannabinoid system during epileptogenesis and indicates that the CB(1) receptor redistribution temporally correlates with the emergence of epileptic seizures...
  27. ncbi Muscarinic acetylcholine receptors: mutant mice provide new insights for drug development
    Jurgen Wess
    Molecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland 20892 0810, USA
    Nat Rev Drug Discov 6:721-33. 2007
    ..Importantly, these studies have identified specific mAChR-regulated pathways as potentially novel targets for the treatment of various important disorders including Alzheimer's disease, schizophrenia, pain, obesity and diabetes...
  28. ncbi Signaling cascades implicated in muscarinic regulation of proliferation of neural stem and progenitor cells
    Wu Ma
    Center for Bio Molecular Science and Engineering, Naval Research Laboratory, Washington DC, USA
    Drug News Perspect 17:258-66. 2004
    ..The mitogenic effects of muscarinic agonists are likely mediated via mAChR-activated multisignaling pathways...
  29. ncbi Novel persistent activation of muscarinic M1 receptors by xanomeline
    A Christopoulos
    Division of Neuroscience Research in Psychiatry, University of Minnesota Medical School, Minneapolis 55455, USA
    Eur J Pharmacol 334:R3-4. 1997
    The muscarinic agonists, xanomeline and carbachol, displayed similar intrinsic activities in stimulating neuronal nitric oxide synthase at muscarinic M1 receptors in Chinese hamster ovary (CHO) cells, with xanomeline being more potent...
  30. pmc Phospholipase C activator m-3M3FBS affects Ca2+ homeostasis independently of phospholipase C activation
    Jelena Krjukova
    Division of Physiology, Department of Neuroscience, Uppsala University, BMC, PO Box 572, SE 75123 Uppsala, Sweden
    Br J Pharmacol 143:3-7. 2004
    ..m-3M3FBS also interfered with store-operated Ca(2+) influx and Ca(2+) extrusion. In conclusion, m-3M3FBS cannot be considered either potent or specific PLC activator...
  31. ncbi Distinct pathways of ERK activation by the muscarinic agonists pilocarpine and carbachol in a human salivary cell line
    Alan L Lin
    Department of Dental Diagnostic Science, University of Texas Health Science Center, San Antonio, TX, USA
    Am J Physiol Cell Physiol 294:C1454-64. 2008
    ..We examined the activation of ERK1/2 by two muscarinic agonists, pilocarpine and carbachol, in a human salivary cell line (HSY)...
  32. ncbi Cholinergic inhibition of neocortical pyramidal neurons
    Allan T Gulledge
    Division of Neuroscience, John Curtin School of Medical Research, Australian National University, Canberra, Australia
    J Neurosci 25:10308-20. 2005
    ..These data demonstrate that acetylcholine can directly inhibit the output of neocortical pyramidal neurons...
  33. ncbi Pharmacological and functional characterization of muscarinic receptor subtypes in developing oligodendrocytes
    F Ragheb
    Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada
    J Neurochem 77:1396-406. 2001
    ..Functional consequences of these events are a reduction in carbachol-stimulated p42/44(MAPK) and CREB phosphorylation, as well as induction of c-fos...
  34. ncbi M1 muscarinic agonists target major hallmarks of Alzheimer's disease--an update
    Abraham Fisher
    Israel Institute for Biological Research, P O Box 19, 74100 Ness Ziona, Israel
    Curr Alzheimer Res 4:577-80. 2007
    ..g. cholinergic deficiency, cognitive dysfunctions, beta-amyloid (Abeta) and tau pathologies. Some muscarinic agonists, while effective in AD, had limited clinical value due to adverse effects and lack of M1 selectivity...
  35. ncbi AF150(S) and AF267B: M1 muscarinic agonists as innovative therapies for Alzheimer's disease
    Abraham Fisher
    Israel Institute for Biological Research, Ness Ziona
    J Mol Neurosci 19:145-53. 2002
    The M1 muscarinic agonists AF102B (Cevimeline, EVOXACTM: prescribed in USA and Japan for Sjogren's Syndrome), AF150(S) and AF267B--1) are neurotrophic and synergistic with neurotrophins such as nerve growth factor and epidermal growth ..
  36. ncbi Muscarinic acetylcholine receptor knockout mice: novel phenotypes and clinical implications
    Jurgen Wess
    Molecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, DHHS, Bethesda, Maryland 20892, USA
    Annu Rev Pharmacol Toxicol 44:423-50. 2004
    ..The novel insights gained from these studies should prove instrumental for the development of novel classes of muscarinic drugs...
  37. pmc Memory enhancement induced by post-training intrabasolateral amygdala infusions of beta-adrenergic or muscarinic agonists requires activation of dopamine receptors: Involvement of right, but not left, basolateral amygdala
    Ryan T Lalumiere
    Department of Neurobiology and Behavior, University of California, Irvine, CA 92697, USA
    Learn Mem 12:527-32. 2005
    ..Additionally, these findings indicate that the enhancement, but not impairment, of memory consolidation is lateralized to the right BLA...
  38. pmc Activation of muscle nicotinic acetylcholine receptor channels by nicotinic and muscarinic agonists
    G Akk
    Department of Physiology and Biophysics, State University of New York, Buffalo, New York, NY 14214, USA
    Br J Pharmacol 128:1467-76. 1999
    ..The results are discussed in terms of structure-function relationships at the nAChR transmitter binding site...
  39. ncbi Influence of muscarinic agonists and tyrosine kinase inhibitors on L-type Ca(2+)Channels in human and bovine trabecular meshwork cells
    K Steinhausen
    Institut für Klinische Physiologie, Universitatsklinikum Benjamin Franklin, Freie Universitat Berlin, Hindenburgdamm 30, Berlin, 12200, Germany
    Exp Eye Res 70:285-93. 2000
    ..The activity of L-type Ca(2+)currents is influenced by muscarinic agonists and tyrosine kinases.
  40. ncbi Functional characterization of cardiomyocytes derived from murine induced pluripotent stem cells in vitro
    Alexey Kuzmenkin
    Institute for Neurophysiology, Medical Center, University of Cologne, Cologne, Germany
    FASEB J 23:4168-80. 2009
    ..This difference may reflect the incomplete reprogramming of iPS cells and should be critically considered in further studies to clarify the suitability of the iPS model for regenerative medicine of heart disorders...
  41. ncbi M1 muscarinic agonists target major hallmarks of Alzheimer's disease--the pivotal role of brain M1 receptors
    Abraham Fisher
    Israel Institute for Biological Research, Ness Ziona, Israel
    Neurodegener Dis 5:237-40. 2008
    ..M1 muscarinic receptor (M1 mAChR) is a therapeutic target in Alzheimer's disease (AD) and the M1-selective muscarinic agonists AF102B, AF150(S) and AF267B are cognitive enhancers and potential disease modifiers...
  42. ncbi Reconstitution of muscarinic modulation of the KCNQ2/KCNQ3 K(+) channels that underlie the neuronal M current
    M S Shapiro
    Department of Physiology, University of Washington School of Medicine, Seattle, Washington 98195, USA
    J Neurosci 20:1710-21. 2000
    ..The M current is modulated by muscarinic agonists via G-proteins and an unidentified diffusible cytoplasmic messenger...
  43. pmc Muscarinic modulation of erg potassium current
    Wiebke Hirdes
    Department of Physiology and Biophysics, University of Washington School of Medicine, G 424 Health Sciences Building, Box 357290, Seattle, WA 98195 7290, USA
    J Physiol 559:67-84. 2004
    ..Wortmannin did not prevent muscarinic inhibition. Our studies of muscarinic inhibition of erg current suggest a role for phospholipase C, but not the classical downstream messengers, such as PKC or a calcium transient...
  44. ncbi Thoracic leg motoneurons in the isolated CNS of adult Manduca produce patterned activity in response to pilocarpine, which is distinct from that produced in larvae
    Rebecca M Johnston
    Department of Neurobiology, University of Arizona, Tucson AZ 85721 0077, USA
    Invert Neurosci 4:175-92. 2002
    ..Nevertheless, the basic similarity to adult walking and clear distinctions from the larval fictive crawling pattern suggest that changes within the CNS contribute to alterations in locomotor activity during metamorphosis...
  45. pmc Defects in muscarinic receptor-coupled signal transduction in isolated parotid gland cells after in vivo irradiation: evidence for a non-DNA target of radiation
    R P Coppes
    Department of Radiation and Stress Cell Biology, University of Groningen, Ant Deusinglaan 1, 9713 AV Groningen, The Netherlands
    Br J Cancer 92:539-46. 2005
    ..To the best of our knowledge, these data for the first time suggest that, the cells' capacity to respond to a receptor agonist is impaired after irradiation...
  46. ncbi Distinct muscarinic receptors enhance spontaneous GABA release and inhibit electrically evoked GABAergic synaptic transmission in the chick lateral spiriform nucleus
    J Guo
    Department of Pharmacology, School of Medicine and Health Sciences, The George Washington University, 2300 Eye Street N W, Washington, DC 20037, USA
    Neuroscience 104:1057-66. 2001
    The effects of muscarinic agonists on GABAergic synaptic transmission were examined using whole-cell patch-clamp recording in chick brain slices containing the lateral spiriform nucleus...
  47. ncbi The M2 muscarinic receptor mediates contraction through indirect mechanisms in mouse urinary bladder
    Frederick J Ehlert
    Department of Pharmacology, College of Medicine, University of California Irvine, Irvine, CA 92697 4625, USA
    J Pharmacol Exp Ther 313:368-78. 2005
    ..We also show that it is difficult to detect M2 receptor function in competitive antagonism studies under conditions where a simultaneous activation of M2 and M3 receptors occurs...
  48. ncbi Constitutive activity and inverse agonism at the M2 muscarinic acetylcholine receptor
    Carl P Nelson
    Department of Cell Physiology and Pharmacology, University of Leicester, University Road, Leicester LE1 9HN, UK
    J Pharmacol Exp Ther 316:279-88. 2006
    ..This indicates that the N410Y mutation of the M(2) mACh receptor alters receptor-G-protein coupling in an agonist-dependent manner, in addition to generating a constitutively active receptor phenotype...
  49. ncbi Role of dopamine D1 receptors in the striatal and cortical fos expression induced by the muscarinic agonist pilocarpine
    David Wirtshafter
    Laboratory of Integrative Neuroscience, Department of Psychology, University of Illinois at Chicago, 1007 West Harrison, Chicago, IL 60607 7137, USA
    Eur J Pharmacol 488:85-90. 2004
    ..75-3.00 mg/kg) virtually abolished the Fos response at both sites. These results suggest that stimulation of dopamine D1 receptors may mediate the effects of muscarinic agonists on Fos expression in the striatum, but not the cortex.
  50. ncbi A single point mutation (N514Y) in the human M3 muscarinic acetylcholine receptor reveals differences in the properties of antagonists: evidence for differential inverse agonism
    Mark R Dowling
    Department of Cell Physiology and Pharmacology, Maurice Shock Medical Sciences Building, University of Leicester, University Road, Leicester, LE1 9HN, UK
    J Pharmacol Exp Ther 317:1134-42. 2006
    ....
  51. ncbi Presynaptic muscarinic receptor subtypes involved in the enhancement of spontaneous GABAergic postsynaptic currents in hippocampal neurons
    J C Gonzalez
    Instituto Teofilo Hernando, IIS Hospital Universitario de la Princesa, Facultad de Medicina, Universidad Autonoma de Madrid, Madrid, Spain
    Eur J Neurosci 33:69-81. 2011
    ....
  52. ncbi The effects of tertiapin-Q on responses of the sinoatrial pacemaker of the guinea-pig heart to vagal nerve stimulation and muscarinic agonists
    Chris P Bolter
    Department of Physiology, School of Medical Sciences, University of Otago, PO Box 913, Dunedin 9054, New Zealand
    Exp Physiol 93:53-63. 2008
    ..IK,ACh, in the bradycardia produced by electrical stimulation of the vagus (parasympathetic) nerve and muscarinic agonists (ACh and bethanecol, bolus i.a.)...
  53. pmc No evidence for a role of muscarinic M2 receptors in functional antagonism in bovine trachea
    A F Roffel
    Groningen Utrecht Institute for Drug Exploration, Department of Medicinal Chemistry and Molecular Pharmacology, University of Groningen, The Netherlands
    Br J Pharmacol 115:665-71. 1995
    ..Furthermore,they stress the importance of taking into account non-cholinergic controls as well as contraction levels in these experiments...
  54. pmc Discovery and characterization of novel allosteric potentiators of M1 muscarinic receptors reveals multiple modes of activity
    Joy E Marlo
    Department of Pharmacology, Vanderbilt University, Nashville, Tennessee 37232, USA
    Mol Pharmacol 75:577-88. 2009
    ..These data also suggest that structurally diverse M(1) potentiators may act by distinct mechanisms and differentially regulate receptor coupling to downstream signaling pathways...
  55. pmc Modulation of high-voltage activated Ca(2+) channels by membrane phosphatidylinositol 4,5-bisphosphate
    Byung Chang Suh
    Department of Physiology and Biophysics, The University of Washington School of Medicine, Seattle, WA 98195 7290, USA
    Neuron 67:224-38. 2010
    ..Thus, endogenous membrane PIP(2) supports high-voltage activated L-, N-, and P/Q-type Ca(2+) channels, and stimuli that activate phospholipase C deplete PIP(2) and reduce those Ca(2+) channel currents...
  56. ncbi Dendritic but not somatic GABAergic inhibition is decreased in experimental epilepsy
    R Cossart
    INMED, , Avenue de Luminy, B.P. 13, 13 273 Marseille Cedex 09, France
    Nat Neurosci 4:52-62. 2001
    ..A deficit in dendritic inhibition could reduce seizure threshold, whereas enhanced somatic inhibition would prevent the continuous occurrence of epileptiform activity...
  57. ncbi Regulation of Kv7 (KCNQ) K+ channel open probability by phosphatidylinositol 4,5-bisphosphate
    Yang Li
    Department of Physiology, University of Texas Health Science Center, San Antonio, Texas 78229, USA
    J Neurosci 25:9825-35. 2005
    ..Divergent apparent affinities of Kv7.2-7.4 channels for PIP2 may underlie their highly differential maximal Po observed in cell-attached patches...
  58. pmc Survival of dentate hilar mossy cells after pilocarpine-induced seizures and their synchronized burst discharges with area CA3 pyramidal cells
    H E Scharfman
    Center for Neural Recovery and Rehabilitation Research, Helen Hayes Hospital, West Haverstraw, NY 10993 1195, USA
    Neuroscience 104:741-59. 2001
    ..The fact that mossy cells have epileptiform bursts, and that they are synchronized with area CA3, suggest a previously unappreciated substrate for hyperexcitability in this animal model...
  59. ncbi Cholinergic targets for cognitive enhancement in schizophrenia: focus on cholinesterase inhibitors and muscarinic agonists
    Joseph I Friedman
    Department of Psychiatry, The Mount Sinai School of Medicine, One Gustave L Levy Place, Box 1230, New York, NY 10029, USA
    Psychopharmacology (Berl) 174:45-53. 2004
    ..Therefore, pharmacological treatments that enhance central cholinergic function may be useful as cognitive enhancers in schizophrenia...
  60. pmc In vivo and in vitro effects of pilocarpine: relevance to ictogenesis
    Nicola Marchi
    Department of Cerebrovascular Research, The Cleveland Clinic Foundation, Cleveland, Ohio 44195, USA
    Epilepsia 48:1934-46. 2007
    ..The extent of such peripheral events and the contribution to SE are unknown and the possibility that pilocarpine also induces SE by peripheral actions is yet untested...
  61. ncbi Reassessment of the effects of cycloheximide on mossy fiber sprouting and epileptogenesis in the pilocarpine model of temporal lobe epilepsy
    Philip A Williams
    Department of Biomedical Sciences, Anatomy and Neurobiology Section, Colorado State University, Fort Collins, Colorado 80523, USA
    J Neurophysiol 88:2075-87. 2002
    ..However, the develoment of spontaneous motor seizures, in a small number of rats, could occur without detectable hippocampal neuron loss or mossy fiber sprouting, as assessed by the Timm stain method...
  62. ncbi Cholinergic control of firing pattern and neurotransmission in rat neostriatal projection neurons: role of CaV2.1 and CaV2.2 Ca2+ channels
    Tamara Perez-Rosello
    Departamento de Biofisica, Instituto de Fisiologia Celular, Universidad Nacional Autonoma de Mexico, Mexico City DF, Mexico
    J Neurophysiol 93:2507-19. 2005
    ..Together, both effects would tend to recruit more spiny neurons for the same task...
  63. ncbi Muscarinic receptor subtype pharmacology and physiology
    Richard M Eglen
    DiscoveRx Corporation, Albrae Street, Fremont, CA 94538, USA
    Prog Med Chem 43:105-36. 2005
  64. ncbi Salivary gland dysfunction: a review of systemic therapies
    M M Grisius
    Department of Oral Medicine, University of Pennsylvania School of Dental Medicine, Philadelphia 19104 6003, USA
    Oral Surg Oral Med Oral Pathol Oral Radiol Endod 92:156-62. 2001
    ..The aim of this article is to briefly review salivary gland physiology and to summarize the suggested systemic treatment modalities for xerostomia that emphasize controlled clinical trials...
  65. ncbi FRET-based sensors for the human M1-, M3-, and M5-acetylcholine receptors
    Nicole Ziegler
    Department of Pharmacology and Toxicology, University of Wuerzburg, Versbacher Str 9, 97078 Wuerzburg, Germany
    Bioorg Med Chem 19:1048-54. 2011
    ..Taken together our data support the notion that orthosteric agonists behave similar at different muscarinic receptor subtypes but that kinetic differences can be observed for receptor activation...
  66. pmc Muscarinic facilitation of GABA release in substantia gelatinosa of the rat spinal dorsal horn
    H Baba
    Department of Anaesthesiology, Niigata University School of Medicine, Niigata 951, Japan
    J Physiol 508:83-93. 1998
    ..Those effects may be responsible for the antinociceptive action produced by the intrathecal administration of muscarinic agonists and acetylcholinesterase inhibitors.
  67. ncbi Preemptive pharmacologic intervention in radiation-induced salivary dysfunction
    S E Taylor
    Department of Oral and Maxillofacial Surgery and Pharmacology, Baylor College of Dentistry The Texas A and M University System, Dallas, Texas 75246, USA
    Proc Soc Exp Biol Med 221:14-26. 1999
    ..Finally, we describe encouraging results from early clinical trials suggesting that protection of salivary glands during therapeutic irradiation may be possible...
  68. ncbi Muscarinic agonists for the treatment of cognition in schizophrenia
    Angela K Sellin
    Department of Psychiatry, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA
    CNS Spectr 13:985-96. 2008
    ..We present an overview of likely side effects of muscarinic agonists. We outline the anticholinergic activity of several available antipsychotics and review the available M1 ..
  69. pmc Dual effects of muscarinic M(2) acetylcholine receptors on the synthesis of cyclic AMP in CHO cells: dependence on time, receptor density and receptor agonists
    P Michal
    Institute of Physiology, Academy of Sciences of the Czech Republic, Videnska 1083, 14220 Prague, Czech Republic
    Br J Pharmacol 132:1217-28. 2001
    ..It tends to be abolished by receptor internalization...
  70. pmc Subtype-selective allosteric modulators of muscarinic receptors for the treatment of CNS disorders
    P Jeffrey Conn
    Department of Pharmacology, Vanderbilt Program in Drug Discovery, Vanderbilt Medical Center, Nashville, TN 37232, USA
    Trends Pharmacol Sci 30:148-55. 2009
    ....
  71. ncbi Muscarinic acetylcholine neurotransmission enhances the late-phase of long-term potentiation in the hippocampal-prefrontal cortex pathway of rats in vivo: a possible involvement of monoaminergic systems
    C Lopes Aguiar
    Department of Neurology, Psychiatry and Medical Psychology, Ribeirao Preto School of Medicine, University of Sao Paulo, Avenida Bandeirantes 3900, Ribeirao Preto, SP, Brazil
    Neuroscience 153:1309-19. 2008
    ..Our data, therefore, suggest that muscarinic activation exerts a boosting effect on mPFC synaptic plasticity and possibly on mPFC-dependent memories, associated to monoaminergic changes...
  72. pmc Impaired M3 and enhanced M2 muscarinic receptor contractile function in a streptozotocin model of mouse diabetic urinary bladder
    K J Pak
    Department of Pharmacology, School of Medicine, University of California, Irvine, CA 92697 4625, USA
    Naunyn Schmiedebergs Arch Pharmacol 381:441-54. 2010
    ..M2 receptor activation opposes forskolin-induced relaxation of the urinary bladder, and this M(2) function is enhanced following streptozotocin treatment...
  73. ncbi Determination of [35S]guanosine-5'-O-(3-thio)triphosphate binding mediated by cholinergic muscarinic receptors in membranes from Chinese hamster ovary cells and rat striatum using an anti-G protein scintillation proximity assay
    N W Delapp
    Lilly Research Laboratories, Eli Lilly and Company, Indianapolis, Indiana, USA
    J Pharmacol Exp Ther 289:946-55. 1999
    ..Antibody capture GTPgamma35S binding using scintillation proximity assay technology provides a convenient, productive alternative to immunoprecipitation for exploration of receptor-G protein interaction in cells and tissues...
  74. ncbi Differences in kinetics of xanomeline binding and selectivity of activation of G proteins at M(1) and M(2) muscarinic acetylcholine receptors
    Jan Jakubik
    Department of Neurochemistry, Institute of Physiology CAS, Videnska 1083, 14220 Prague, Czech Republic
    Mol Pharmacol 70:656-66. 2006
    ..These conformations are both time- and concentration-dependent and vary between the M(1) and the M(2) receptor...
  75. ncbi Muscarinic agonists acting through M2 acetylcholine receptors stimulate the migration of an NO-sensitive guanylyl cyclase to the plasma membrane of bovine tracheal smooth muscle
    Fabiola Pláceres Uray
    Sección de Biomembranas, Instituto de Medicina Experimental, Cátedra de Patología General y Fisiopatología, Escuela Luis Razetti, Facultad de Medicina Universidad Central de Venezuela, Caracas, Venezuela
    J Recept Signal Transduct Res 30:10-23. 2010
    b>Muscarinic agonists acting on bovine tracheal smooth muscle (BTSM) induce two separate cGMP signals, one at 20 sec associated with NO-sensitive-soluble-guanylyl-cyclase (NO-sGC) and another at 60 sec, linked to natriuretic-peptide-GC...
  76. ncbi Pilocarpine prevents age-related spatial learning impairments in rats
    Nelson De-Mello
    Departamento de Farmacologia, CCB, Universidade Federal de Santa Catarina, Campus Universitario Trindade, 88049 900 Florianopolis, SC, Brazil
    Behav Brain Res 158:263-8. 2005
    ..These results indicate that a single administration of Pilo might prevent the age-related learning impairments in rats on a spatial task in the water maze...
  77. ncbi Long-term changes in the muscarinic M1 receptor induced by instantaneous formation of wash-resistant xanomeline-receptor complex
    Kayla C De Lorme
    Division of Neuroscience Research in Psychiatry, University of Minnesota Medical School, Minneapolis, MN 55455, USA
    J Pharmacol Exp Ther 323:868-76. 2007
    ..Our results imply that brief exposure to xanomeline followed by washing and prolonged waiting may result in delayed receptor desensitization accompanied by internalization or down-regulation...
  78. ncbi Gender comparison of muscarinic receptor expression and function in rat and human urinary bladder: differential regulation of M2 and M3 receptors?
    Christian Kories
    Department of Medicine, University of Essen, Germany
    Naunyn Schmiedebergs Arch Pharmacol 367:524-31. 2003
    ....
  79. ncbi Muscarinic acetylcholine receptors as CNS drug targets
    Christopher J Langmead
    Psychiatry Centre of Excellence for Drug Discovery, GlaxoSmithKline, Third Avenue, Harlow, Essex, CM19 5AW, UK
    Pharmacol Ther 117:232-43. 2008
    ....
  80. ncbi Activation of the cholinergic system endows compositional properties to striatal cell assemblies
    Luis Carrillo-Reid
    Departamento de Biofisica, Instituto de Fisiologia Celular, Universidad Nacional Autónoma de México UNAM PO Box 70 253, Mexico City, DF 04510 Mexico
    J Neurophysiol 101:737-49. 2009
    ..Neuronal recurrent networks with the characteristics encountered in the present experiments are proposed to allow repeated sequences of activity to become memories and repeated memories to compose learned motor procedures...
  81. ncbi Identification of a ligand-dependent switch within a muscarinic receptor
    T A Spalding
    ACADIA Pharmaceuticals, Inc, San Diego, California 92121, USA
    J Biol Chem 273:21563-8. 1998
    ..These results suggest that TM6 is a switch that defines the activation state of the receptor, and that ligand interactions with TM6 stabilize the receptor in either an active or an inactive conformation...
  82. ncbi Imaging of muscarinic acetylcholine receptor signaling in hippocampal neurons: evidence for phosphorylation-dependent and -independent regulation by G-protein-coupled receptor kinases
    Jonathon M Willets
    Department of Cell Physiology and Pharmacology, University of Leicester, Leicester LE1 9HN, United Kingdom
    J Neurosci 24:4157-62. 2004
    ..Together, our data suggest a role for both phosphorylation-dependent and -independent regulation of M1 mACh receptors in hippocampal neurons...
  83. pmc The guinea pig ileum lacks the direct, high-potency, M(2)-muscarinic, contractile mechanism characteristic of the mouse ileum
    Michael T Griffin
    Department of Chemistry, Chapman University, Orange, CA, USA
    Naunyn Schmiedebergs Arch Pharmacol 380:327-35. 2009
    ..The guinea pig ileum, therefore, lacks a direct, highly potent, M(2)-contractile component but may have a direct, lower potency M(2) component...
  84. pmc Regulation of bladder muscarinic receptor subtypes by experimental pathologies
    M R Ruggieri
    Department of Urology, Temple University, Philadelphia, PA, USA
    Auton Autacoid Pharmacol 26:311-25. 2006
    ..This finding has substantial implications for the clinical treatment of abnormal bladder contractions...
  85. ncbi Homologous mutations near the junction of the sixth transmembrane domain and the third extracellular loop lead to constitutive activity and enhanced agonist affinity at all muscarinic receptor subtypes
    Diane J Ford
    Department of Pharmacology, The Pennsylvania State University College of Medicine, Hershey, Pennsylvania 17033, USA
    J Pharmacol Exp Ther 300:810-7. 2002
    ..Based on the results of the present study, it is possible that TM6 represents a general switch for the activation of the muscarinic receptor family...
  86. ncbi Effects of Ba-Wei-Die-Huang-Wan on the cholinergic function and protein expression of M2 muscarinic receptor of the urinary bladder in diabetic rats
    Yat Ching Tong
    Department of Urology, College of Medicine, National Cheng Kung University, Tainan City, 70101, Taiwan, ROC
    Neurosci Lett 330:21-4. 2002
    ..In conclusion, there was an over-expression of M(2) receptor resulting in hyper-contractility in the bladder of diabetic rats. Ba-Wei-Die-Huang-Wan significantly alleviated the alterations...
  87. ncbi Allosteric modulation by persistent binding of xanomeline of the interaction of competitive ligands with the M1 muscarinic acetylcholine receptor
    Jan Jakubik
    Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic
    J Pharmacol Exp Ther 301:1033-41. 2002
    ..Our findings are best interpreted in terms of allosteric interactions between xanomeline-persistent binding to the M(1) muscarinic receptor and competitive ligands bound to the classical receptor binding site...
  88. ncbi Subunit-specific modulation of KCNQ potassium channels by Src tyrosine kinase
    Nikita Gamper
    Department of Physiology, University of Texas Health Science Center at San Antonio, San Antonio, Texas 78229, USA
    J Neurosci 23:84-95. 2003
    ..Finally, experiments using cloned KCNQ2/3 channels, Src and M(1) muscarinic receptors, and sympathetic neurons demonstrated that the actions on KCNQ channels by Src and by muscarinic agonists use distinct mechanisms.
  89. ncbi Discovery of an ectopic activation site on the M(1) muscarinic receptor
    Tracy A Spalding
    ACADIA Pharmaceuticals, Inc, San Diego, California 92121, USA
    Mol Pharmacol 61:1297-302. 2002
    ....
  90. ncbi A critical role for beta cell M3 muscarinic acetylcholine receptors in regulating insulin release and blood glucose homeostasis in vivo
    Dinesh Gautam
    Molecular Signaling Section, Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892, USA
    Cell Metab 3:449-61. 2006
    ..These findings indicate that beta cell M3 muscarinic receptors play a key role in maintaining proper insulin release and glucose homeostasis...
  91. pmc Differential regulation of muscarinic M1 receptors by orthosteric and allosteric ligands
    Christopher N Davis
    ACADIA Pharmaceuticals Inc, 3911 Sorrento Valley Blvd, San Diego, CA 92121, USA
    BMC Pharmacol 9:14. 2009
    ..The focus of the present study was to determine if M1 receptors activated by allosteric agonists undergo the same regulatory fate as M1 receptors activated by orthosteric agonists...
  92. ncbi Regulation of muscarinic acetylcholine receptor signaling
    Chris J van Koppen
    Institut fur Pharmakologie, Universitatsklinikum Essen, Hufelandstrasse 55, D 45122, Essen, Germany
    Pharmacol Ther 98:197-220. 2003
    ..In this review, our current understanding of the complex regulatory processes that underlie signaling of mAChR is summarized...
  93. ncbi Experiments to test the role of phosphatidylinositol 4,5-bisphosphate in neurotransmitter-induced M-channel closure in bullfrog sympathetic neurons
    Christopher P Ford
    Centre for Neuroscience, University of Alberta, Edmonton, Alberta, Canada T6G 2H7
    J Neurosci 23:4931-41. 2003
    ..These are the results that might be expected if agonist-induced activation of PLC and the concomitant depletion of PIP2 contribute to the excitatory action of neurotransmitters that suppress gM...
  94. ncbi M1 muscarinic agonists can modulate some of the hallmarks in Alzheimer's disease: implications in future therapy
    Abraham Fisher
    Israel Institute for Biological Research, 74100 Ness Ziona, Israel
    J Mol Neurosci 20:349-56. 2003
    ..We evaluated the M1 muscarinic agonists AF102B (Cevimeline, EVOXAC trade mark : prescribed for Sjøgren's syndrome), AF150(S), and AF267B on some ..
  95. ncbi Cyclicity of spontaneous recurrent seizures in pilocarpine model of temporal lobe epilepsy in rat
    Karolien Goffin
    Katholieke Universiteit Leuven, Leuven, Belgium
    Exp Neurol 205:501-5. 2007
    ..Finally, our data suggest that the model can be used for studies aiming at identifying the mechanisms of seizure clustering...
  96. pmc Long-term wash-resistant effects of brief interaction of xanomeline at the M1 muscarinic receptor
    Kayla C De Lorme
    Division of Neuroscience Research in Psychiatry, University of Minnesota Medical School, Mayo Mail Code 392, 420 Delaware St SE, Minneapolis, MN 55455, USA
    Neurosci Lett 410:11-4. 2006
    ..However, possible involvement of other mechanisms of long-term receptor regulation cannot be discounted...
  97. ncbi Effect of urothelium on bladder contractility in diabetic rats
    Murat Kosan
    Second Urology Clinic, Ankara Numune Education and Research Hospital, Ankara, Turkey
    Int J Urol 12:677-82. 2005
    ..It is known that physiopathological changes in diabetes affect the function of the bladder. In this study, we aimed to demonstrate the possible effects of diabetes on the urothelium during this physiopathological process...
  98. ncbi Structural requirements of transmembrane domain 3 for activation by the M1 muscarinic receptor agonists AC-42, AC-260584, clozapine, and N-desmethylclozapine: evidence for three distinct modes of receptor activation
    Tracy A Spalding
    ACADIA Pharmaceuticals, Inc, 3911 Sorrento Valley Boulevard, San Diego, CA 92121, USA
    Mol Pharmacol 70:1974-83. 2006
    ..crucial role mediating muscarinic acetylcholine receptor activation by acetylcholine, carbachol, and other muscarinic agonists. We compared the effects of point mutations throughout TM3 on the interactions of carbachol, 4-n-butyl-1-[4-..
  99. ncbi Probing the molecular mechanism of interaction between 4-n-butyl-1-[4-(2-methylphenyl)-4-oxo-1-butyl]-piperidine (AC-42) and the muscarinic M(1) receptor: direct pharmacological evidence that AC-42 is an allosteric agonist
    Christopher J Langmead
    Psychiatry Centre of Excellence for Drug Discovery, GlaxoSmithKline, Third Ave, Harlow, Essex, CM19 5AW, UK
    Mol Pharmacol 69:236-46. 2006
    ..These data provide the first direct evidence that AC-42 is an allosteric agonist that activates M(1) receptors in the absence of the orthosteric agonist...
  100. ncbi Muscarinic receptor function, density and G-protein coupling in the overactive diabetic rat bladder
    L A Stevens
    Biomedical Research Centre, Sheffield Hallam University, Sheffield S1 1WB, UK
    Auton Autacoid Pharmacol 26:303-9. 2006
    1 Bladder smooth muscle sensitivity to muscarinic agonists is increased in the overactive bladder...
  101. ncbi On the physiological relevance of muscarinic acetylcholine receptors in Alzheimer's disease
    H J Koch
    University Clinic of Neurology, Universitatsstrasse 84, 93053 Regensburg, Germany
    Curr Med Chem 12:2915-21. 2005
    ..Experimental results postulate a positive long lasting modulation of the pathological neuronal protein pattern in addition to their cholinomimetic effect...

Research Grants63

  1. Atrial Fibrillation in Hyperthyroidism: Active Antibodies to Autonomic Receptors
    DAVID KEM; Fiscal Year: 2013
    ..Adrenergic and muscarinic agonists are known to enhance the likelihood for developing AF...
  2. Molecular mechanism of regulation of mI(CAT) in intestinal smooth muscle cells
    Michael X Zhu; Fiscal Year: 2012
    ..In the smooth muscle cells, co-stimulation of M2R and M3R by muscarinic agonists activates a cation current, mICAT...
  3. Atypical Antipsychotics: Effects on Hepatic Glucose and Lipid Metabolism in Human
    Michael R Rickels; Fiscal Year: 2012
    ..Findings from these studies will have important clinical relevance to the treatment of schizophrenia. ..
  4. An Animal Model of Diabetic Autonomic Neuropathy: Study of Mechanism and Therapy
    JONAS BERNARD GALPER; Fiscal Year: 2010
    ..This model offers a unique opportunity for new insights into mechanism and therapy of DAN and its relationship to arrhythmia and sudden death. ..
  5. The Contribution of Melanocyte-like Cells to Atrial Function and Development
    Vickas V Patel; Fiscal Year: 2013
    ....
  6. The neurogenic potential of cholinergic activation in AD.
    ELIZABETH ADAMS ECKMAN; Fiscal Year: 2013
    ..Early preliminary data indicate that muscarinic agonists do indeed increase cytogenesis in a manner very similar to that initially observed with D3 agonist ..
  7. Mechanisms and behavioral relevance of reward timing in the primary visual cortex
    EMMA BERYL ROACH; Fiscal Year: 2010
    ..This knowledge is highly important to the study of learning and decision-making, both under normal circumstances and in maladaptive states such as drug addiction. ..
  8. Selective Muscarinic Receptor Ligands as Targets for Cocaine Addiction Medication
    MORGANE MARIE THOMSEN; Fiscal Year: 2013
    ..gene knockout technology to evaluate which muscarinic receptor subtypes mediate anti-cocaine effects of muscarinic agonists, and which mediate undesirable effects...
  9. Prostanoid Modulators that Reduce Brain Injury After Seizures
    Raymond J Dingledine; Fiscal Year: 2013
    ..We intend to create novel drugs that target inflammation pathways to minimize the brain damage and cognitive deficits that accompany prolonged seizures.. ..
  10. NEW MUSCARINIC AGENTS--SELECTIVITY OF ACTION
    Frank Carroll; Fiscal Year: 1990
    ..The development of new, more effective, selective and less toxic cholinergic and anticholinergic drugs is of interest due to the possible therapeutic exploitation of the cholinergic hypothesis of Alzheimer's disease...
  11. REGULATION OF GLANDULAR MUCOUS CELL SECRETION
    DAVID CULP; Fiscal Year: 2001
    ..Results will provide specific information for determination of the dose and temporal administration of agonist in future clinical trials to treat patients with salivary hypofunction. ..
  12. BRAIN PHOSPHOINOSITIDES AND BARBITURATES
    DIWAKAR DESHMUKH; Fiscal Year: 1993
    ..the mobilization of calcium resulting from stimulation of synaptosomes or synaptoneurosomes by cholinergic muscarinic agonists, and of platelets by thrombin will be measured as diminished release of Ca from the intracellular membranes,..
  13. AUTONOMIC RECEPTOR FUNCTION IN LV HYPERTROPHY & FAILURE
    Dorothy Vatner; Fiscal Year: 1991
    ..It is proposed that these studies will enhance our understanding at the cellular level, of one of the most important problems in clinical cardiology, i.e., left ventricular hypertrophy and heart failure...
  14. AUTONOMIC MUSCARINIC RECEPTOR SIGNALING MECHANISMS
    FRED EHLERT; Fiscal Year: 2000
    ..known that the M3 muscarinic receptor elicits contraction in a variety of smooth muscles which respond to muscarinic agonists, yet the most abundant subtype of the muscarinic receptor is the M2, accounting for approximately 80% of ..
  15. CELLULAR AND MOLECULAR STUDIES OF VESTIBULAR HAIR CELLS
    MANNING CORREIA; Fiscal Year: 2007
    ..The two specific aims of this project are linked in that one drives studies of the the effector pKir2.1 and the second directs studies the msucarinic receptors in the pathway proposed above. ..
  16. CHOLINERGIC MECHANISMS IN AGING AND AD
    LINCOLN POTTER; Fiscal Year: 2002
    ..hemi-PD, but is expected to alter responses to apomorphine (dopamine agonist), pilocarpine and xanomeline (muscarinic agonists). At the least, the results will show whether a specific m1 antagonist can be used to control seizures...
  17. Regulation of Airway Goblet Cell Mucin Secretion
    C Davis; Fiscal Year: 2007
    ..For instance, the effects of muscarinic agonists are highly controversial, there are no data relevant to the mechanisms and pathways underlying the ..
  18. DERMAL CHOLINERGIC RECEPTORS AND ALZHEIMER'S DISEASE
    HELENA RYER; Fiscal Year: 1992
    ..To this end, any changes found in dermal cholinergic function will be evaluated for the degree to which they are correlated with the severity of dementia found in AD subjects or are associated with early or late onset AD...
  19. Muscarinic regulation of plasticity in the brain
    Gene Robinson; Fiscal Year: 2009
    ..Our results will also suggest directions for the development of treatments for the decline in mental function that accompanies human aging. ..
  20. INTERACTION OF DRUGS WITH BRAIN ACETYLCHOLINE
    DONALD JENDEN; Fiscal Year: 1992
    ..be investigated in the same tissues by measuring changes in phosphatidylinositol turnover in response to muscarinic agonists, partial agonists and antagonists...
  21. MECHANISMS OF MUSCARINIC RECEPTOR CROSS-TALK IN BRAIN
    FRED EHLERT; Fiscal Year: 1993
    ..using pharmacological null methods and radioligand binding methods to analyze the properties of selective muscarinic agonists and antagonists...
  22. REGULATION OF CALCIUM CHANNELS BY PROTEIN KINASE C
    Robert Messing; Fiscal Year: 1990
    ..b>Muscarinic agonists also activate protein kinase C, by stimulating phosphoinositide hydrolysis and diacylglycerol production, ..
  23. PHOSPHOLIPASES AND INSULIN SECRETION
    Bryan Wolf; Fiscal Year: 1999
    ..Simultaneously, stimulation of the beta-cell by fuel secretagogues or muscarinic agonists activates phospholipases C and A2, which are enzymes that hydrolyze phospholipids to generate lipid second ..
  24. AMYLOIDOGENIC EFFECTS OF CHOLINERGIC DENERVATION
    Thomas Beach; Fiscal Year: 2002
    ..This could lead to impaired cerebral vasoregulation and increased susceptibility to ischemia, further compromising cortical function in AD. ..
  25. MUSCARINIC RECEPTOR COUPLING MECHANISMS IN THE BRAIN
    FRED EHLERT; Fiscal Year: 1992
    ..Consequently, the ability of muscarinic agonists to potentiate or modulate the effects which other neurotransmitters, drugs and peptides have on cyclic AMP ..
  26. CARDIOVASCULAR CELL GENE TRANSFER OF ADENYLYL CYCLASE
    Paul Insel; Fiscal Year: 2003
    ....
  27. ION CHANNELS AND AIRWAY SMOOTH MUSCLE ACTIVATION
    Cornelis van Breemen; Fiscal Year: 1991
    ....
  28. Utility of Muscarinic Agonists for Alzheimer's disease
    Edward McGuire; Fiscal Year: 2005
    ..The proposed work will allow Cognitive Pharmaceuticals, Ltd. to reach a major milestone in the commercialization of CDD-0102 for the treatment of Alzheimer's disease. ..
  29. ROLE OF PROTEIN PHOSPHORYLATION IN CULTURED HEART CELLS
    Bruce Liang; Fiscal Year: 1990
    ....
  30. Novel Signaling for Ca2+ and Release in Airway Myocytes
    Yong Xiao Wang; Fiscal Year: 2007
    ..hyper-functioned in asthma, contributing to the airway muscle Ca2+ and contractile hyperresponsiveness to muscarinic agonists and other numerous spasomogens...
  31. MUSCARINIC RECEPTORS/G-PROTEINS IN EARLY AD
    Pamela Potter; Fiscal Year: 1999
    ..abstract_text> ..
  32. Utility of Muscarinic Agonists in Schizopherenia
    Edward McGuire; Fiscal Year: 2005
    ..Together, the proposed studies will identify a lead compound to move into full preclinical development for the treatment of cognitive deficits and other symptoms associated with schizophrenia. ..
  33. PHARMACOLOGY OF DEVELOPING CARDIAC TISSUES
    Achilles Pappano; Fiscal Year: 2000
    ..inhibitor of cGMP-production, LY83583 or pertussis toxin to determine the role of cGMP inhibition by muscarinic agonists. In the aim A3 the applicant will study the role of protein phosphatase in the inhibition of Ica and ..
  34. Nicotinic-Purinergic Modulation of Bladder Contraction
    George Somogyi; Fiscal Year: 2009
    ..This interaction can be evoked by mixed nicotinic-muscarinic agonists like carbachol, or the cholinergic transmitter acetylcholine, indicating that this finding may have ..
  35. Molecular Basis of K+ Current During Secretion
    Keith Nehrke; Fiscal Year: 2002
    ..chloride channel on the apical membrane, and these channels work together to allow stimulated secretion by muscarinic agonists. The molecular identity of each of these channels remains unknown...
  36. Cholesterol Effects on Caveolin-G Protein Interactions
    Jeremiah Kelly; Fiscal Year: 2001
    ..abstract_text> ..
  37. EFFECTS OF THE SENSORY NERVE SYSTEM ON BLADDER FUNCTION
    Reginald Bruskewitz; Fiscal Year: 1993
    ..This information will be of significant value in medical treatment of uninhibited bladder contractions...
  38. Role of M4 mAChR in Modulating Hippocampal Neurotransmission
    JANA SHIREY; Fiscal Year: 2009
    ..b>Muscarinic agonists have a number of electrophysiological effects in the hippocampus including potentiation of NMDA receptor ..
  39. MUSCARINIC CHOLINERGIC RECEPTORS IN THE HEART
    NEIL NATHANSON; Fiscal Year: 2000
    ..Recent work from Dr. Nathanson's laboratory has demonstrated that treatment of chick heart cells with muscarinic agonists and transforming growth factor-beta regulates the expression of mRNAs encoding the two main mAChR subtypes ..
  40. SOMATOSTATIN RELATED PEPTIDES AND BRAIN FUNCTION
    GEORGE SIGGINS; Fiscal Year: 2003
    ..neurons (HPNs) by augmenting two K+ conductances: the M-current (Im) and the leak current (Ilk); muscarinic agonists block both these currents; 2) arachidonic acid (AA) metabolites mediate these SST K+ channel effects; 3) ..
  41. TYROSINE PHOSPHORYLATION IN MUSCARINIC SIGNALLING
    Jeanclare Seagrave; Fiscal Year: 1993
    ..proteins of the submandibular gland acinar cells are involved in the biochemical cascade that occurs when muscarinic agonists interact with cholinergic receptors in the membranes of these cells...
  42. MUSCARINIC RECEPTOR SIGNALING
    ESAM EL FAKAHANY; Fiscal Year: 2006
    ..Thus, xanomeline-like muscarinic agonists are considered promising candidates for drug development for cholinergic replacement therapy in Alzeimer&..
  43. Utility of Muscarinic Agonists for Alzheimer's disease
    DEBASIS GHOSH; Fiscal Year: 2002
    The purpose of the present study is to assess the utility of muscarinic agonists in treating Alzheimer's disease. Levels of acetylcholine decrease in Alzheimer's disease, resulting in memory deficits...
  44. ELECTROPHYSIOLOGICAL STUDY OF MUSCARINIC ACTIONS IN CNS
    THOMAS PITLER; Fiscal Year: 1992
    ..Several electrophysiological responses to muscarinic agonists will be studied using intracellular techniques (current-clamp and single-electrode voltage-clamp) in the ..
  45. CELLULAR MECHANISMS OF CRACK COCAINES CARDIAC TOXICITY
    James Morgan; Fiscal Year: 2000
    ....
  46. AIRWAY SMOOTH MUSCLE IN HEALTH AND DISEASE
    RONALD COBURN; Fiscal Year: 2004
    ..In particular, all of these diseases cause physiological alterations that influence the length at which smooth muscle cells contract and relax. ..
  47. CALCIUM AND CURRENT RESPONSES TO AGONISTS
    Stuart Thompson; Fiscal Year: 1993
    ..b>Muscarinic agonists, and other ligands, initiate (Ca)i oscillations in N1E-115 cells...
  48. PHARMACOLOGY OF AQUEOUS OUTFLOW IN THE HUMAN EYE
    Kristine Erickson; Fiscal Year: 2000
    ..mediating the responsiveness of the outflow system to such diverse stimuli as epinephrine, prostaglandins, muscarinic agonists and modulators of Na/K/2Cl co-transport...
  49. PATHOGENESIS OF HYPERTENSIVE CARDIOVASCULAR DISEASE
    JOSEPH WIENER; Fiscal Year: 1992
    ..generation of cyclic nucleotides; 3) to measure the biological activity of relaxing substance released by muscarinic agonists from cerebral cortical microvessels, and determine how the release of this relaxing substance is modulated ..
  50. CHOLINERGIC REGULATION OF INTESTINAL POTASSIUM TRANSPORT
    Michael Duffey; Fiscal Year: 1992
    ..4) Integrated response: We will determine whether a hyperpolarization of membrane voltage and intracellular Ca2+ oscillations are part of the Cl- secretory response of intact tissues during cholinergic stimulation...
  51. DESIGN OF NEW BENZODIAZEPINE LIGANDS AS MEMORY ENHANCERS
    TIMOTHY DELOREY; Fiscal Year: 2000
    ..strategies have focused on the drug-induced increase in the activity of cholinergic neurons by the use of muscarinic agonists and cholinesterase inhibitors...
  52. Dopamine & Ach regulation of inhibition in PFC
    Jeremy Seamans; Fiscal Year: 2005
    ..Specifically, Ach muscarinic antagonists eliminated the D2-mediated reduction in IPSCs while muscarinic agonists mimicked the D2 effect...
  53. Development of a Selective Muscarinic Agonist for the Treatment of Schizophrenia
    TREVOR TWOSE; Fiscal Year: 2009
    The overall goal of the proposed research is to develop selective muscarinic agonists for the treatment of psychosis and cognitive dysfunction associated with schizophrenia...
  54. TRANSMITTER MODULATION OF REPOLARIZATION IN HEART
    Erwin Shibata; Fiscal Year: 1992
    ..by further exploring the nature and the possible second messengers of the potassium current induced by muscarinic agonists, and by identifying the types of potassium current present in a mammalian model for human myocardium: the ..
  55. Regulation of mAChR Function and Expression
    DARRELL JACKSON; Fiscal Year: 2006
    ..induces phosphorylation of the m2 mAChR, thereby leading to internalization and decreased responsiveness to muscarinic agonists. In Specific Aim 2, experiments will be conducted to test the hypothesis that desensitization of the m2 ..
  56. Agonist Activity at G Protein Coupled Receptors
    FRED EHLERT; Fiscal Year: 2008
    ..Our proposed investigation of Galpha15 and Galpha16 is highly significant with regard to the widespread use of this G protein as a transducer for both orphan and known receptors. ..
  57. Cholinergic modulation of IEG expression
    ANN POWER; Fiscal Year: 2006
    ..Experiment III will investigate which signaling cascades (e.g., protein kinases) are involved in effects of mR activation on memory and immediate early gene expression. ..
  58. Muscarinic agonists for neurological disorders
    William Messer; Fiscal Year: 2007
    ..b>Muscarinic agonists might be helpful in restoring the chemical imbalances in cholinergic activity associated with neurological ..
  59. Forebrain-Cerebellar Interaction During Learning
    John Disterhoft; Fiscal Year: 2008
    ..The data gathered here will also be useful for understanding and treating deficits in learning and memory in young and aging persons. ..
  60. GSK3beta: Signaling and apoptosis
    RICHARD JOPE; Fiscal Year: 2007
    ..Overall, these experiments will clarify mechanisms regulating GSK3b and its effects on neural plasticity and survival. ..
  61. PKC modulation of calcium current and anesthetic action
    GANESAN KAMATCHI; Fiscal Year: 2007
    ..abstract_text> ..
  62. BASAL GANGLIA CIRCUITRY IMMEDIATE EARLY GENE EXPRESSION
    David Wirtshafter; Fiscal Year: 2003
    ..Other studies will examine the effects of lesions within the basal ganglia on the IEG expression induced by systemic administration of dopaminergic drugs. ..