Genomes and Genes
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.
Publications267 found, 100 shown here
- Muscarinic acetylcholine receptor knockout mice: novel phenotypes and clinical implicationsJurgen 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...
- New insights from the use of pilocarpine and kainate modelsJ 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...
- AKAP150 signaling complex promotes suppression of the M-current by muscarinic agonistsNaoto 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...
- Muscarine reduces calcium-dependent electrical activity in substantia nigra dopaminergic neuronsR S Scroggs
Department of Anatomy and Neurobiology, Health Science Center, University of Tennessee, Memphis, Tennessee 38163, USA
J Neurophysiol 86:2966-72. 2001....
- 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 assayN 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...
- Origin of spontaneous activity in neonatal and adult rat bladders and its enhancement by stretch and muscarinic agonistsA 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...
- Cholinergic inhibition of neocortical pyramidal neuronsAllan 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...
- Constitutive activity and inverse agonism at the M2 muscarinic acetylcholine receptorCarl 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...
- The effects of tertiapin-Q on responses of the sinoatrial pacemaker of the guinea-pig heart to vagal nerve stimulation and muscarinic agonistsChris 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.)...
- The M2 muscarinic receptor mediates contraction through indirect mechanisms in mouse urinary bladderFrederick 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...
- Preemptive pharmacologic intervention in radiation-induced salivary dysfunctionS 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...
- Impaired M3 and enhanced M2 muscarinic receptor contractile function in a streptozotocin model of mouse diabetic urinary bladderK 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...
- No evidence for a role of muscarinic M2 receptors in functional antagonism in bovine tracheaA 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...
- Cholinergic treatments with emphasis on m1 muscarinic agonists as potential disease-modifying agents for Alzheimer's diseaseAbraham 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...
- Salivary gland dysfunction: a review of systemic therapiesM 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...
- Distinct muscarinic receptors enhance spontaneous GABA release and inhibit electrically evoked GABAergic synaptic transmission in the chick lateral spiriform nucleusJ 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. 2001The 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...
- Role of dopamine D1 receptors in the striatal and cortical fos expression induced by the muscarinic agonist pilocarpineDavid 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.
- Presynaptic muscarinic receptor subtypes involved in the enhancement of spontaneous GABAergic postsynaptic currents in hippocampal neuronsJ 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....
- FRET-based sensors for the human M1-, M3-, and M5-acetylcholine receptorsNicole 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...
- Muscarinic agonists for the treatment of cognition in schizophreniaAngela 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 ..
- A single point mutation (N514Y) in the human M3 muscarinic acetylcholine receptor reveals differences in the properties of antagonists: evidence for differential inverse agonismMark 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....
- Discovery and characterization of novel allosteric potentiators of M1 muscarinic receptors reveals multiple modes of activityJoy 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...
- Temporal characterization of changes in hippocampal cannabinoid CB(1) receptor expression following pilocarpine-induced status epilepticusKatherine 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...
- Dual effects of muscarinic M(2) acetylcholine receptors on the synthesis of cyclic AMP in CHO cells: dependence on time, receptor density and receptor agonistsP 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...
- Muscarinic acetylcholine receptors: mutant mice provide new insights for drug developmentJurgen 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...
- Two distinct classes of muscarinic action on hippocampal inhibitory synapses: M2-mediated direct suppression and M1/M3-mediated indirect suppression through endocannabinoid signallingYuko 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...
- Subtype-selective allosteric modulators of muscarinic receptors for the treatment of CNS disordersP Jeffrey Conn
Department of Pharmacology, Vanderbilt Program in Drug Discovery, Vanderbilt Medical Center, Nashville, TN 37232, USA
Trends Pharmacol Sci 30:148-55. 2009....
- In vivo and in vitro effects of pilocarpine: relevance to ictogenesisNicola 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...
- Muscarinic acetylcholine receptors as CNS drug targetsChristopher J Langmead
Psychiatry Centre of Excellence for Drug Discovery, GlaxoSmithKline, Third Avenue, Harlow, Essex, CM19 5AW, UK
Pharmacol Ther 117:232-43. 2008....
- Activation of the cholinergic system endows compositional properties to striatal cell assembliesLuis 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...
- Identification of a ligand-dependent switch within a muscarinic receptorT 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...
- 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....
- Pilocarpine prevents age-related spatial learning impairments in ratsNelson De-Mello
Departamento de Farmacologia, CCB, Universidade Federal de Santa Catarina, , , 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...
- Reconstitution of muscarinic modulation of the KCNQ2/KCNQ3 K(+) channels that underlie the neuronal M currentM 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...
- Imaging of muscarinic acetylcholine receptor signaling in hippocampal neurons: evidence for phosphorylation-dependent and -independent regulation by G-protein-coupled receptor kinasesJonathon 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...
- Long-term changes in the muscarinic M1 receptor induced by instantaneous formation of wash-resistant xanomeline-receptor complexKayla 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...
- 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 amygdalaRyan 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...
- Survival of dentate hilar mossy cells after pilocarpine-induced seizures and their synchronized burst discharges with area CA3 pyramidal cellsH 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...
- Differential coupling of muscarinic M1, M2, and M3 receptors to phosphoinositide hydrolysis in urinary bladder and longitudinal muscle of the ileum of the mouseJohn A Tran
Department of Pharmacology, College of Medicine, University of California, Irvine, CA 92697-4625, USA
J Pharmacol Exp Ther 318:649-56. 2006..These data suggest a major role for the M3 receptor in eliciting phosphoinositide hydrolysis in the ileum and urinary bladder and minor roles for the M1 and M2 in ileum...
- Reduction of cerebrospinal fluid amyloid beta after systemic administration of M1 muscarinic agonistsT G Beach
Sun Health Research Institute, 10515 Santa Fe Drive, Sun City, AZ 85372, USA
Brain Res 905:220-3. 2001..Systemic administration of 3 M1-selective muscarinic agonists, AF102B, AF150S and AF267B, decreased cerebrospinal fluid (CSF) A beta concentrations; levels of CSF ..
- Therapeutic strategies in Alzheimer's disease: M1 muscarinic agonistsA 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 ..
- Inhibition of KCNQ1-4 potassium channels expressed in mammalian cells via M1 muscarinic acetylcholine receptorsA A Selyanko
Department of Pharmacology, University College London, UK
J Physiol 522:349-55. 2000..4. It is concluded that M1 receptors couple to all known KCNQ subunits and that inhibition of KCNQ2 + KCNQ3 channels, like that of native M-channels, requires a diffusible second messenger...
- 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 agonistChristopher 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...
- Regulation of Kv7 (KCNQ) K+ channel open probability by phosphatidylinositol 4,5-bisphosphateYang 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...
- On the physiological relevance of muscarinic acetylcholine receptors in Alzheimer's diseaseH 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...
- 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 activationTracy 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-..
- Repeated low-dose treatment of rats with pilocarpine: low mortality but high proportion of rats developing epilepsyM Glien
Department of Pharmacology, Toxicology and Pharmacy, School of Veterinary Medicine, , D-30559 Hannover, Germany
Epilepsy Res 46:111-9. 2001..The present study demonstrates that systemic treatment of lithium-pretreated rats with several low doses of pilocarpine efficiently produces SE and chronic epilepsy with much lower mortality rates than single-dose pilocarpine...
- Effect of urothelium on bladder contractility in diabetic ratsMurat 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...
- M1 muscarinic agonists can modulate some of the hallmarks in Alzheimer's disease: implications in future therapyAbraham 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 ..
- Postsynaptic M1 and M3 receptors are responsible for the muscarinic enhancement of retrograde endocannabinoid signalling in the hippocampusTakako 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...
- Experiments to test the role of phosphatidylinositol 4,5-bisphosphate in neurotransmitter-induced M-channel closure in bullfrog sympathetic neuronsChristopher 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...
- Regulation of muscarinic acetylcholine receptor signalingChris 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...
- Role of receptor protein and membrane lipids in xanomeline wash-resistant binding to muscarinic M1 receptorsJan Jakubik
Institute of Physiology, Academy of Sciences of the Czech Republic, Prague
J Pharmacol Exp Ther 308:105-10. 2004..We suggest that the binding of xanomeline involves interhelical penetration of M1 muscarinic receptor by xanomeline's O-alkyl chain and interaction with membrane lipids surrounding the receptor...
- Cholinergic targets for cognitive enhancement in schizophrenia: focus on cholinesterase inhibitors and muscarinic agonistsJoseph 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...
- Subunit-specific modulation of KCNQ potassium channels by Src tyrosine kinaseNikita 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.
- Effects of Ba-Wei-Die-Huang-Wan on the cholinergic function and protein expression of M2 muscarinic receptor of the urinary bladder in diabetic ratsYat 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...
- Recovery from muscarinic modulation of M current channels requires phosphatidylinositol 4,5-bisphosphate synthesisByung-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...
- Allosteric modulation by persistent binding of xanomeline of the interaction of competitive ligands with the M1 muscarinic acetylcholine receptorJan 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...
- Discovery of an ectopic activation site on the M(1) muscarinic receptorTracy A Spalding
ACADIA Pharmaceuticals, Inc, San Diego, California 92121, USA
Mol Pharmacol 61:1297-302. 2002....
- Nuclear calcium signaling evoked by cholinergic stimulation in hippocampal CA1 pyramidal neuronsJohn 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...
- Regulation of acetylcholine release by muscarinic receptors at the mouse neuromuscular junction depends on the activity of acetylcholinesteraseJasmina Minic
Institut Fédératif de Neurobiologie Alfred Fessard, Laboratoire de Neurobiologie Cellulaire et Moleculaire, C N R S, U P R 9040, 1 Avenue de la Terrasse, 91198 Gif sur Yvette Cedex, France
Eur J Neurosci 15:439-48. 2002....
- 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 subtypesDiane 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...
- NMDA-receptor regulation of muscarinic-receptor stimulated inositol 1,4,5-trisphosphate production and protein kinase C activation in single cerebellar granule neuronsKenneth W Young
Department of Cell Physiology and Pharmacology, University of Leicester, Medical Sciences Building, University Road, Leicester LE1 9HN, UK
J Neurochem 89:1537-46. 2004..Thus, NMDA-mediated Ca2+ influx and PLC activation may represent a coincident-detection system whereby ionotropic and metabotropic signals combine to stimulate InsP(3) production and PKC-mediated phosphorylation events in CGNs...
- Cholinergic dilation of cerebral blood vessels is abolished in M(5) muscarinic acetylcholine receptor knockout miceM 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....
- Relationship between membrane phosphatidylinositol-4,5-bisphosphate and receptor-mediated inhibition of native neuronal M channelsJoanna 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....
- Muscarinic agonist-mediated heterologous desensitization in isolated ileum requires activation of both muscarinic M2 and M3 receptorsMichael T Griffin
Department of Physical Sciences, Chapman University, Orange, California, USA
J Pharmacol Exp Ther 308:339-49. 2004....
- A critical role for beta cell M3 muscarinic acetylcholine receptors in regulating insulin release and blood glucose homeostasis in vivoDinesh 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...
- Two-state models and the analysis of the allosteric effect of gallamine at the M2 muscarinic receptorFrederick J Ehlert
Department of Pharmacology, School of Medicine, University of California, Irvine, CA 92697 4625, USA
J Pharmacol Exp Ther 325:1039-60. 2008..If it is assumed that allosterism occurs at the relay site and not the activation site, then this model can account for affinity-only modulation in a manner consistent with the allosteric ternary complex model...
- Insulin, IGF-1, and muscarinic agonists modulate schizophrenia-associated genes in human neuroblastoma cellsC Anthony Altar
Psychiatric Genomics, Inc, Gaithersburg, Maryland, USA
Biol Psychiatry 64:1077-87. 2008..We determined with human SH-SY5Y neuroblastoma and astrocyte cell lines whether insulin or other molecules could modulate genes opposite to their change reported in schizophrenia brain...
- Xanomeline compared to other muscarinic agents on stimulation of phosphoinositide hydrolysis in vivo and other cholinomimetic effectsF P Bymaster
Lilly Neuroscience Research, Lilly Research Laboratories, Lilly Corporate Center, Indianapolis, IN 46285, USA
Brain Res 795:179-90. 1998..to stimulate in vivo phosphoinositide (PI) hydrolysis and compared it to a number of direct acting muscarinic agonists, two cholinesterase inhibitors and a putative m1 agonist/muscarinic m2 antagonist...
- On the unique binding and activating properties of xanomeline at the M1 muscarinic acetylcholine receptorA Christopoulos
Division of Neuroscience Research in Psychiatry, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA
Mol Pharmacol 53:1120-30. 1998....
- Diabetes mellitus and responses of the urinary bladder to acetylcholine: an in vitro studyAbdon M Nsabimana
Department of Pharmacology, School of Pharmacy and Pharmacology, Faculty of Health Sciences, University of KwaZulu Natal, Durban, South Africa
J Smooth Muscle Res 44:143-50. 2008..on the responses of diabetic bladder strips to cholinergic nerve stimulation or exogenously-administered muscarinic agonists, especially acetylcholine (ACh)...
- G protein coupling and signaling pathway activation by m1 muscarinic acetylcholine receptor orthosteric and allosteric agonistsRachel L Thomas
Department of Cell Physiology and Pharmacology, University of Leicester, Room 4 04, Henry Wellcome Building, Lancaster Road, Leicester LE19HN, UK
J Pharmacol Exp Ther 327:365-74. 2008..77-LH-28-1 (1-[3-(4-butyl-1-piperidinyl)propyl]-3,4-dihydro-2(1H)-quinolinone), and a range of orthosteric muscarinic agonists [oxotremorine-M (oxo-M), arecoline, and pilocarpine] in Chinese hamster ovary cells recombinantly ..
- Activation of muscarinic acetylcholine receptors via their allosteric binding sitesJ Jakubik
Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic
Proc Natl Acad Sci U S A 93:8705-9. 1996..of the classical-binding sites of these receptors and either diminish or increase their affinity for muscarinic agonists and classical antagonists...
- Selective muscarinic receptor agonist xanomeline as a novel treatment approach for schizophreniaAnantha Shekhar
Department of Psychiatry, Indiana University School of Medicine, 1111 West 10th St, Suite 313, Indianapolis, IN 46202, USA
Am J Psychiatry 165:1033-9. 2008..The authors studied xanomeline, a relatively selective muscarinic type 1 and type 4 (M(1) and M(4)) receptor agonist, to determine if this agent is effective in the treatment of schizophrenia...
- Human muscarinic receptors expressed in A9L and CHO cells: activation by full and partial agonistsM H Richards
Marion Merrell Dow Research Center, Strasbourg, France
Br J Pharmacol 114:1241-9. 19951. A comparative study of receptor activation by ten full and partial muscarinic agonists was undertaken on the five subtypes of human muscarinic receptors expressed at similar receptor densities in Chinese hamster ovary (CHO-K1) cells...
- Novel persistent activation of muscarinic M1 receptors by xanomelineA Christopoulos
Division of Neuroscience Research in Psychiatry, University of Minnesota Medical School, Minneapolis 55455, USA
Eur J Pharmacol 334:R3-4. 1997The 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...
- Characterization of a CNS penetrant, selective M1 muscarinic receptor agonist, 77-LH-28-1C J Langmead
Psychiatry Centre of Excellence for Drug Discovery, GlaxoSmithKline, Harlow, Essex, UK
Br J Pharmacol 154:1104-15. 2008..However, studies with this compound have been limited to recombinantly expressed mAChRs...
- Cyclicity of spontaneous recurrent seizures in pilocarpine model of temporal lobe epilepsy in ratKarolien 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...
- Effects of an agonist, allosteric modulator, and antagonist on guanosine-gamma-[35S]thiotriphosphate binding to liposomes with varying muscarinic receptor/Go protein stoichiometryJ Jakubik
Institute of Physiology, Academy of Sciences of the Czech Republic, 14220 Prague, Czechia
Mol Pharmacol 54:899-906. 1998..This suggests that the receptors and G proteins are located in microdomains in which their concentrations remain constant, despite variations in the amounts of lipidic membranes in the system...
- Long-term wash-resistant effects of brief interaction of xanomeline at the M1 muscarinic receptorKayla 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...
- The guinea pig ileum lacks the direct, high-potency, M(2)-muscarinic, contractile mechanism characteristic of the mouse ileumMichael 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...
- Assessment of the progressive nature of cell damage in the pilocarpine model of epilepsyL Covolan
Departamento de Fisiologia, , , SP, Brasil
Braz J Med Biol Res 39:915-24. 2006..As a consequence of both mechanisms, subsequent insults after an initial insult result in very little damage regardless of their intensity...
- Three distinct muscarinic signalling pathways for cationic channel activation in mouse gut smooth muscle cellsTakashi Sakamoto
Department of Pathogenetic Veterinary Science, United Graduate School of Veterinary Science, Gifu University, 1 1 Yanagido, Gifu 501 1193, Japan
J Physiol 582:41-61. 2007..The delineation of this pathway is consistent with the formation of a functional unit by the M2-Go protein and the M3-PLC systems predicted to control cationic channels...
- Muscarinic receptor function, density and G-protein coupling in the overactive diabetic rat bladderL A Stevens
Biomedical Research Centre, Sheffield Hallam University, Sheffield S1 1WB, UK
Auton Autacoid Pharmacol 26:303-9. 20061 Bladder smooth muscle sensitivity to muscarinic agonists is increased in the overactive bladder...
- Differential regulation of muscarinic M1 receptors by orthosteric and allosteric ligandsChristopher 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...
- Regulation of bladder muscarinic receptor subtypes by experimental pathologiesM 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...
- Acute induction of epileptiform discharges by pilocarpine in the in vitro isolated guinea-pig brain requires enhancement of blood-brain barrier permeabilityL 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...
- Muscarinic M3 receptor inactivation reveals a pertussis toxin-sensitive contractile response in the guinea pig colon: evidence for M2/M3 receptor interactionsG W Sawyer
Department of Pharmacology, College of Medicine, University of California, Irvine, USA
J Pharmacol Exp Ther 289:464-76. 1999..This model predicts that a response mediated by both the M2 and M3 receptor can be pertussis toxin sensitive yet exhibit an antagonistic profile indicative of an M3 response...
- Cholinergic regulation of the evoked quantal release at frog neuromuscular junctionEugeny E Nikolsky
Institute of Biochemistry and Biophysics, Russian Academy of Sciences, Kazan, Russia
J Physiol 560:77-88. 2004..The muscarinic agonists, oxotremorine and the propargyl ester of arecaidine, as well as antagonists such as pirenzepine, AF-DX 116 ..
- Both endogenous and exogenous ACh plays antinociceptive role in the hippocampus CA1 of ratsX F Yang
Department of Physiology, Harbin Medical University, Harbin, China
J Neural Transm 115:1-6. 2008..5 microg/1 microl) produced opposite response. On the basis of the above findings, we can deduce that ACh and mAChRs are involved in the modulation of nociceptive information transmission in the hippocampal CA1...
- PMA decreases the proliferation of retinal cells in vitro: the involvement of acetylcholine and BDNFAline Araujo dos Santos
Programa de Neuroimunologia, Departamento de Neurobiologia, Instituto de Biologia, Centro de Estudos Gerais, Universidade Federal Fluminense, , Rio de Janeiro 24001-970, Brazil
Neurochem Int 42:73-80. 2003..Our results suggest that PKC activation leads to a decrease in retinal cells proliferation through the release of acetylcholine and brain derived neurotrophic factor in the culture, and activation of M1 and TrkB receptors, respectively...
- Role of muscarinic acetylcholine receptors in a guinea pig model of asthmaYuji Tohda
Fourth Department of Internal Medicine, Kinki University School of Medicine, Osakasayama, Osaka, Japan
Int Immunopharmacol 2:1521-7. 2002..These results suggest that, in OA-sensitized guinea pigs, a dysfunction of M2R leads to the abnormal density of M3R...
- Subtype-specific regulation of the expression and function of muscarinic acetylcholine receptors in embryonic chicken retinal cellsJuan C Goin
Department of Pharmacology, University of Washington School of Medicine, Seattle, Washington 98195, USA
J Neurochem 83:964-72. 2002..These data demonstrate subtype-specific regulation of the expression and function of muscarinic receptors in the retina...
- Chronotropic response of beta-adrenergic-, muscarinic-, and calcitonin gene-related peptide-receptor agonists in right atria from neonatal capsaicin-treated ratsAlessandra L Gasparetti
Department of Pharmacology, Faculty of Medical Sciences, UNICAMP, P.O. Box 6111, 13081-970, Campinas (SP, Brazil
Neurosci Lett 325:147-50. 2002..In summary, capsaicin treatment in newborn rats produces a desensitization of chronotropic response mediated by beta-adrenoceptors in isolated right atria from 30-day-old rats possibly due to a massive release of catecholamines...
- Activation of muscarinic acetylcholine receptors elicits pigment granule dispersion in retinal pigment epithelium isolated from bluegillAlfredo Gonzalez
Department of Biology, Texas State University San Marcos, Texas 78666, USA
BMC Neurosci 5:23. 2004..To determine the receptor pathway involved in eliciting pigment granule migration, we isolated retinal pigment epithelium from bluegill and subjected it to a battery of cholinergic agents...
- Synthesis and pharmacology of benzoxazines as highly selective antagonists at M(4) muscarinic receptorsThomas M Böhme
Department of Medicinal Chemistry, Pfizer Global Research and Development, Ann Arbor Laboratories, 2800 Plymouth Road, Ann Arbor, MI 48105, USA
J Med Chem 45:3094-102. 2002..This is evidence that suggests that agonist-induced increase in catecholamine synthesis observed in these regions is mediated by M(4) receptors...
- Multiple muscarinic acetylcholine receptor subtypes modulate striatal dopamine release, as studied with M1-M5 muscarinic receptor knock-out miceWeilie Zhang
Laboratory of Bioorganic Chemistry, National Institutes of Diabetes and Digestive and Kidney Diseases, Bethesda, Maryland 20892 0810, USA
J Neurosci 22:6347-52. 2002..These findings should contribute to a better understanding of the important functional roles that the muscarinic cholinergic system plays in striatal function...
- Muscarinic receptors of the neostriatum--their role in controlling operant behavior in dogsK B Shapovalova
I. P. Pavlov Institute of Physiology, Russian Academy of Sciences, St. Petersburg
Neurosci Behav Physiol 32:389-99. 2002....
- Salivary gland-sparing prophylactic pilocarpine treatment has no effect on tumor regrowth after irradiationR Licht
Department of Radiation and Stress Cell Biology, University of Groningen, 9713 AV Groningen, The Netherlands
Radiat Res 157:596-8. 2002..Use of this drug therefore may lead to therapeutic gain in the treatment of head and neck cancer...
- Effects of N-ethylmaleimide on conformational equilibria in purified cardiac muscarinic receptorsChi Shing Sum
Department of Pharmacology and Faculty of Pharmacy, University of Toronto, Toronto, Ontario M5S 2S2, Canada
J Biol Chem 277:36188-203. 2002..Similarities with constitutively active receptors suggest that R and R* are akin to the inactive and active states, respectively. Purified M(2) receptors therefore appear to exist predominantly in their active state...
- Efficacy of GluR5 Antogonists Against Soman-Induced Seizures and NeuropathologyMARIA BRAGA; Fiscal Year: 2007....
- Atypical Antipsychotics: Effects on Hepatic Glucose and Lipid Metabolism in HumanKaren Teff; Fiscal Year: 2009..Findings from these studies will have important clinical relevance to the treatment of schizophrenia. ..
- Atypical Antipsychotics: Effects on Hepatic Glucose and Lipid Metabolism in HumanKaren L Teff; Fiscal Year: 2010..Findings from these studies will have important clinical relevance to the treatment of schizophrenia. ..
- REGULATION OF GLANDULAR MUCOUS CELL SECRETIONDAVID 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. ..
- CELLULAR AND MOLECULAR STUDIES OF VESTIBULAR HAIR CELLSMANNING 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. ..
- The neurogenic potential of cholinergic activation in AD.Elizabeth Eckman; Fiscal Year: 2009..Early preliminary data indicate that muscarinic agonists do indeed increase cytogenesis in a manner very similar to that initially observed with D3 agonist ..
- The neurogenic potential of cholinergic activation in AD.ELIZABETH ADAMS ECKMAN; Fiscal Year: 2010..Early preliminary data indicate that muscarinic agonists do indeed increase cytogenesis in a manner very similar to that initially observed with D3 agonist ..
- EFFECTS OF LITHIUM ON CHOLINERGIC ACTIVITYRICHARD JOPE; Fiscal Year: 1990..Attainment of these goals will increase our understanding of the effects of lithium that may be related to its therapeutic effect in mania and may generate hypotheses as to the underlying causes of bipolar affective disorders...
- CHOLINERGIC MECHANISMS IN AGING AND ADLINCOLN 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...
- Regulation of Airway Goblet Cell Mucin SecretionC 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 ..
- Prostanoid modulators that reduce brain injury and inflammation after seizuresRaymond Dingledine; Fiscal Year: 2007....
- Muscarinic regulation of plasticity in the brainGene Robinson; Fiscal Year: 2007..Our results will also suggest directions for the development of treatments for the decline in mental function that accompanies human aging. ..
- Muscarinic regulation of plasticity in the brainGene 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. ..
- Molecular mechanism of regulation of mI(CAT) in intestinal smooth muscle cellsMICHAEL ZHU; Fiscal Year: 2009..In the smooth muscle cells, co-stimulation of M2R and M3R by muscarinic agonists activates a cation current, mICAT...