drug receptors

Summary

Summary: Proteins that bind specific drugs with high affinity and trigger intracellular changes influencing the behavior of cells. Drug receptors are generally thought to be receptors for some endogenous substance not otherwise specified.

Top Publications

  1. ncbi KATP channels as molecular sensors of cellular metabolism
    Colin G Nichols
    Department of Cell Biology and Physiology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA
    Nature 440:470-6. 2006
  2. ncbi Truncation of Kir6.2 produces ATP-sensitive K+ channels in the absence of the sulphonylurea receptor
    S J Tucker
    University Laboratory of Physiology, Oxford, UK
    Nature 387:179-83. 1997
  3. ncbi The capsaicin receptor: a heat-activated ion channel in the pain pathway
    M J Caterina
    Department of Cellular and Molecular Pharmacology, University of California, San Francisco 94143 0450, USA
    Nature 389:816-24. 1997
  4. ncbi Adenosine diphosphate as an intracellular regulator of insulin secretion
    C G Nichols
    Department of Cell Biology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Science 272:1785-7. 1996
  5. ncbi Cloning of the beta cell high-affinity sulfonylurea receptor: a regulator of insulin secretion
    L Aguilar-Bryan
    Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030, USA
    Science 268:423-6. 1995
  6. ncbi Mutations in the sulfonylurea receptor gene in familial persistent hyperinsulinemic hypoglycemia of infancy
    P M Thomas
    Department of Medical Specialties, University of Texas M D Anderson Cancer Center, Houston 77030, USA
    Science 268:426-9. 1995
  7. ncbi Sulfonylurea receptor type 1 knock-out mice have intact feeding-stimulated insulin secretion despite marked impairment in their response to glucose
    Chiyo Shiota
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    J Biol Chem 277:37176-83. 2002
  8. ncbi The principle of temperature-dependent gating in cold- and heat-sensitive TRP channels
    Thomas Voets
    Laboratory of Physiology, Campus Gasthuisberg, KU Leuven, B 3000 Leuven, Belgium
    Nature 430:748-54. 2004
  9. ncbi Impaired nociception and pain sensation in mice lacking the capsaicin receptor
    M J Caterina
    Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143 0450, USA
    Science 288:306-13. 2000
  10. ncbi Toward understanding the assembly and structure of KATP channels
    L Aguilar-Bryan
    Department of Cell Biology, Baylor College of Medicine, Houston, Texas, USA
    Physiol Rev 78:227-45. 1998

Detail Information

Publications242 found, 100 shown here

  1. ncbi KATP channels as molecular sensors of cellular metabolism
    Colin G Nichols
    Department of Cell Biology and Physiology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, Missouri 63110, USA
    Nature 440:470-6. 2006
    ..In parallel, the uncovering of disease-causing mutations of K(ATP) has led to an explanation of the molecular basis of disease and, in turn, to a better understanding of the structural basis of channel function...
  2. ncbi Truncation of Kir6.2 produces ATP-sensitive K+ channels in the absence of the sulphonylurea receptor
    S J Tucker
    University Laboratory of Physiology, Oxford, UK
    Nature 387:179-83. 1997
    ..We show here that the primary site at which ATP acts to mediate K-ATP channel inhibition is located on Kir6.2, and that SUR1 is required for sensitivity to sulphonylureas and diazoxide and for activation by Mg-ADP...
  3. ncbi The capsaicin receptor: a heat-activated ion channel in the pain pathway
    M J Caterina
    Department of Cellular and Molecular Pharmacology, University of California, San Francisco 94143 0450, USA
    Nature 389:816-24. 1997
    ..The cloned capsaicin receptor is also activated by increases in temperature in the noxious range, suggesting that it functions as a transducer of painful thermal stimuli in vivo...
  4. ncbi Adenosine diphosphate as an intracellular regulator of insulin secretion
    C G Nichols
    Department of Cell Biology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    Science 272:1785-7. 1996
    ..Thus, by binding to SUR NBF2 and antagonizing ATP inhibition of KATP++ channels, intracellular MgADP may regulate insulin secretion...
  5. ncbi Cloning of the beta cell high-affinity sulfonylurea receptor: a regulator of insulin secretion
    L Aguilar-Bryan
    Department of Cell Biology, Baylor College of Medicine, Houston, TX 77030, USA
    Science 268:423-6. 1995
    ..The results suggest that the sulfonylurea receptor may sense changes in ATP and ADP concentration, affect KATP channel activity, and thereby modulate insulin release...
  6. ncbi Mutations in the sulfonylurea receptor gene in familial persistent hyperinsulinemic hypoglycemia of infancy
    P M Thomas
    Department of Medical Specialties, University of Texas M D Anderson Cancer Center, Houston 77030, USA
    Science 268:426-9. 1995
    ..Both mutations resulted in aberrant processing of the RNA sequence and disruption of the putative second nucleotide binding domain of the SUR protein. Abnormal insulin secretion in PHHI appears to be caused by mutations in the SUR gene...
  7. ncbi Sulfonylurea receptor type 1 knock-out mice have intact feeding-stimulated insulin secretion despite marked impairment in their response to glucose
    Chiyo Shiota
    Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, Tennessee 37232, USA
    J Biol Chem 277:37176-83. 2002
    ....
  8. ncbi The principle of temperature-dependent gating in cold- and heat-sensitive TRP channels
    Thomas Voets
    Laboratory of Physiology, Campus Gasthuisberg, KU Leuven, B 3000 Leuven, Belgium
    Nature 430:748-54. 2004
    ..Our results suggest a simple unifying principle that explains both cold and heat sensitivity in TRP channels...
  9. ncbi Impaired nociception and pain sensation in mice lacking the capsaicin receptor
    M J Caterina
    Department of Cellular and Molecular Pharmacology, University of California, San Francisco, San Francisco, CA 94143 0450, USA
    Science 288:306-13. 2000
    ..Thus, VR1 is essential for selective modalities of pain sensation and for tissue injury-induced thermal hyperalgesia...
  10. ncbi Toward understanding the assembly and structure of KATP channels
    L Aguilar-Bryan
    Department of Cell Biology, Baylor College of Medicine, Houston, Texas, USA
    Physiol Rev 78:227-45. 1998
    ..The availability of cloned KATP channel genes opens the way for characterization of this family of ion channels and identification of additional genetic defects...
  11. pmc A mechanism for ATP-sensitive potassium channel diversity: Functional coassembly of two pore-forming subunits
    Y Cui
    Centre for Clinical Pharmacology, Department of Medicine, University College London, The Rayne Institute, 5 University Street, London WC1E 6JJ, United Kingdom
    Proc Natl Acad Sci U S A 98:729-34. 2001
    ..2 or Kir 6.1 expressed with SUR2B. In conclusion, Kir 6.1 and Kir 6.2 readily coassemble to produce functional channels, and such phenomena may contribute to the diversity of nucleotide-regulated potassium currents seen in native tissues...
  12. ncbi Targeted disruption of the Wnk4 gene decreases phosphorylation of Na-Cl cotransporter, increases Na excretion and lowers blood pressure
    Akihito Ohta
    Department of Nephrology, Tokyo Medical and Dental University, Japan
    Hum Mol Genet 18:3978-86. 2009
    ..Thus, wild-type WNK4 is a positive regulator for the WNK-OSR1/SPAK-NCC cascade, and WNK4 is a potential target of anti-hypertensive drugs...
  13. ncbi Hypothalamic K(ATP) channels control hepatic glucose production
    Alessandro Pocai
    Department of Medicine, Diabetes Research Center, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    Nature 434:1026-31. 2005
    ..These findings suggest that activation of hypothalamic K(ATP) channels normally restrains hepatic gluconeogenesis, and that any alteration within this central nervous system/liver circuit can contribute to diabetic hyperglycaemia...
  14. pmc The molecular basis of the specificity of action of K(ATP) channel openers
    C Moreau
    CEA, DBMS, Biophysique Moléculaire et Cellulaire UMR CNRS UJF CEA 5090, 17 rue des Martyrs, 38054 Grenoble, France
    EMBO J 19:6644-51. 2000
    ..This first glimpse of the site of action of pharmacological openers should permit rapid progress towards understanding the structural determinants of their affinity and specificity...
  15. ncbi Functional analysis of capsaicin receptor (vanilloid receptor subtype 1) multimerization and agonist responsiveness using a dominant negative mutation
    E V Kuzhikandathil
    Department of Cell and Molecular Physiology and the Neuroscience Center, University of North Carolina, Chapel Hill, North Carolina 27599, USA
    J Neurosci 21:8697-706. 2001
    ..Analysis of both current density and [(3)H]RTX affinity in cells cotransfected with different ratios of wild-type and mutant VR1 is consistent with tetrameric stoichiometry for the native capsaicin receptor...
  16. ncbi LY320135, a novel cannabinoid CB1 receptor antagonist, unmasks coupling of the CB1 receptor to stimulation of cAMP accumulation
    C C Felder
    Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health, Bethesda, Maryland, USA
    J Pharmacol Exp Ther 284:291-7. 1998
    ..LY320135 is a promising lead compound for the further development of novel, potent and selective cannabinoid antagonists of novel structure...
  17. ncbi ABCC8 and ABCC9: ABC transporters that regulate K+ channels
    Joseph Bryan
    Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA
    Pflugers Arch 453:703-18. 2007
    ..2 polymorphism has been suggested as a predisposing factor in type 2 diabetes mellitus. Studies on K(ATP) channel null mice are clarifying the roles of these metabolically sensitive channels in a variety of tissues...
  18. ncbi Activating mutations in the ABCC8 gene in neonatal diabetes mellitus
    Andrey P Babenko
    Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, USA
    N Engl J Med 355:456-66. 2006
    ..We hypothesized that activating mutations in ABCC8, which encodes SUR1, cause neonatal diabetes...
  19. ncbi Analysis of the native quaternary structure of vanilloid receptor 1
    N Kedei
    Laboratory of Cellular Carcinogenesis and Tumor Promotion, NCI, National Institutes of Health, Bethesda, Maryland 20892, USA
    J Biol Chem 276:28613-9. 2001
    ..Finally, differences in glycosylation between the systems were observed, indicating the need for caution in the use of the heterologous expression systems for analysis of VR1 properties...
  20. ncbi SNPs in the KCNJ11-ABCC8 gene locus are associated with type 2 diabetes and blood pressure levels in the Japanese population
    Yukiko Sakamoto
    Division of Genetic Information, Institute for Genome Research, The University of Tokushima, 3 18 15, Kuramoto Cho, Tokushima City, Tokushima 770 8503, Japan
    J Hum Genet 52:781-93. 2007
    ..8% Japanese), confirmed the significant role of the KCNJ11 E23K variant in T2D susceptibility. Furthermore, we found evidence suggesting that the KCNJ11 E23K genotype is independently associated with higher blood-pressure levels...
  21. pmc WNK kinases regulate thiazide-sensitive Na-Cl cotransport
    Chao Ling Yang
    Division of Nephrology and Hypertension, Department of Medicine, Oregon Health and Science University, Portland, Oregon 97239, USA
    J Clin Invest 111:1039-45. 2003
    ..Together, these results identify WNK kinases as a previously unrecognized sodium regulatory pathway of the distal nephron. This pathway likely contributes to normal and pathological blood pressure homeostasis...
  22. ncbi Association studies of variants in the genes involved in pancreatic beta-cell function in type 2 diabetes in Japanese subjects
    Norihide Yokoi
    Division of Cellular and Molecular Medicine, Kobe University Graduate School of Medicine, Kobe 650 0017, Japan
    Diabetes 55:2379-86. 2006
    ..This is the largest association study so far conducted on these genes in Japanese and provides valuable information for comparison with other ethnic groups...
  23. ncbi Reconstituted human cardiac KATP channels: functional identity with the native channels from the sarcolemma of human ventricular cells
    A P Babenko
    Departments of Cell Biology and Medicine, Baylor College of Medicine, Houston, TX, USA
    Circ Res 83:1132-43. 1998
    ....
  24. ncbi Molecular structure of the glibenclamide binding site of the beta-cell K(ATP) channel
    M V Mikhailov
    Nuffield Department of Clinical Laboratory Sciences, John Radcliffe Hospital, Headington, OX3 9DU, Oxford, UK
    FEBS Lett 499:154-60. 2001
    ..We suggest that in SUR1 in the native K(ATP) channel close proximity of CL3 and CL8 leads to formation of the glibenclamide binding site...
  25. ncbi Ethanol elicits and potentiates nociceptor responses via the vanilloid receptor-1
    M Trevisani
    Department of Experimental and Clinical Medicine, Headache Center, University of Ferrara, via Fossato di Mortara 19, 44100 Ferrara, Italy
    Nat Neurosci 5:546-51. 2002
    ..This provides a likely mechanistic explanation for the ethanol-induced sensory responses that occur at body temperature and for the sensitivity of inflamed tissues to ethanol, such as might be found in esophagitis, neuralgia or wounds...
  26. ncbi Endocannabinoid signaling in the brain
    Rachel I Wilson
    Division of Biology, 139 74, California Institute of Technology, Pasadena, CA 91125, USA
    Science 296:678-82. 2002
    ..Cannabinoids may affect memory, cognition, and pain perception by means of this cellular mechanism...
  27. ncbi Gitelman's variant of Bartter's syndrome, inherited hypokalaemic alkalosis, is caused by mutations in the thiazide-sensitive Na-Cl cotransporter
    D B Simon
    Howard Hughes Medical Institute, Department of Genetics, Boyer Center for Molecular Medicine, New Haven, Connecticut, USA
    Nat Genet 12:24-30. 1996
    ..We speculate that these mutant alleles lead to reduced sodium chloride reabsorption in the more common heterozygotes, potentially protecting against development of hypertension...
  28. pmc Increased ATPase activity produced by mutations at arginine-1380 in nucleotide-binding domain 2 of ABCC8 causes neonatal diabetes
    Heidi de Wet
    Henry Wellcome Centre for Gene Function, Department of Physiology, Anatomy and Genetics, University of Oxford, Parks Road, Oxford OX1 3PT, United Kingdom
    Proc Natl Acad Sci U S A 104:18988-92. 2007
    ..Molecular modeling studies supported this idea. Because mutant channels were inhibited less strongly by MgATP, this would increase K(ATP) currents in pancreatic beta cells, thus reducing insulin secretion and producing diabetes...
  29. pmc Rare independent mutations in renal salt handling genes contribute to blood pressure variation
    Weizhen Ji
    Department of Genetics, Yale University School of Medicine, 333 Cedar Street, New Haven, Connecticut 06510, USA
    Nat Genet 40:592-9. 2008
    ..These findings have implications for the genetic architecture of hypertension and other common complex traits...
  30. pmc AMP-activated protein kinase mediates preconditioning in cardiomyocytes by regulating activity and trafficking of sarcolemmal ATP-sensitive K(+) channels
    Andrey Sukhodub
    Maternal and Child Health Sciences, Ninewells Hospital and Medical School, University of Dundee, Dundee, UK
    J Cell Physiol 210:224-36. 2007
    ....
  31. ncbi A family of sulfonylurea receptors determines the pharmacological properties of ATP-sensitive K+ channels
    N Inagaki
    Division of Molecular Medicine Center for Biomedical Science, Chiba University School of Medicine, Chuo Ku, Chiba 260, Japan
    Neuron 16:1011-7. 1996
    ..The present study shows that the ATP sensitivity and pharmacological properties of K(ATP) channels are determined by a family of structurally related but functionally distinct sulfonylurea receptors...
  32. ncbi Identification of an aspartic residue in the P-loop of the vanilloid receptor that modulates pore properties
    C Garcia-Martinez
    Centro de Biologia Molecular y Celular, Universidad Miguel Hernandez, Elche Alicante 03202, Spain
    J Biol Chem 275:32552-8. 2000
    ....
  33. ncbi K ATP channels of primary human coronary artery endothelial cells consist of a heteromultimeric complex of Kir6.1, Kir6.2, and SUR2B subunits
    Hidetada Yoshida
    Department of Pediatric Cardiology, New York University School of Medicine, 560 First Avenue TCH501, New York, NY 10016, USA
    J Mol Cell Cardiol 37:857-69. 2004
    ..We demonstrate that human coronary endothelial K(ATP) channels consist of a heteromultimeric complex of Kir6.1, Kir6.2, and SUR2B subunits...
  34. ncbi Differential nucleotide regulation of KATP channels by SUR1 and SUR2A
    Ricard Masia
    Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, MO 63110, USA
    J Mol Cell Cardiol 39:491-501. 2005
    ..SUR2A-containing channels, which may in turn contribute to physiological differences, observed at the tissue level, between pancreatic and cardiac K(ATP) channels...
  35. ncbi KATP channel openers: structure-activity relationships and therapeutic potential
    Raimund Mannhold
    Department of Laser Medicine, Molecular Drug Research Group, Heinrich Heine Universitat, Universitatsstrasse 1, 40225 Dusseldorf, Germany
    Med Res Rev 24:213-66. 2004
    ..Examples for new chemical entities more recently developed as KCOs include cyclobutenediones, dihydropyridine related structures, and tertiary carbinols...
  36. ncbi Intrafamilial phenotype variability in patients with Gitelman syndrome having the same mutations in their thiazide-sensitive sodium/chloride cotransporter
    Shih Hua Lin
    Division of Nephrology, Department of Medicine, Tri Service General Hospital, National Defense Medical Center, Taipei, Taiwan
    Am J Kidney Dis 43:304-12. 2004
    ..Although the severity of symptoms may vary in patients who have the same mutations, a markedly different clinical presentation in family members with identical mutations is truly rare...
  37. ncbi cAMP-activated protein kinase-independent potentiation of insulin secretion by cAMP is impaired in SUR1 null islets
    Mitsuhiro Nakazaki
    Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, TX 77030, USA
    Diabetes 51:3440-9. 2002
    ..We hypothesize that a reduced release of insulin in response to incretins may contribute to the unexpected normoglycemic phenotype of Sur1KO mice versus the pronounced hypoglycemia seen in neonates with loss of K(ATP) channel activity...
  38. ncbi A capsaicin-receptor homologue with a high threshold for noxious heat
    M J Caterina
    Department of Cellular and Molecular Pharmacology, University of California, San Francisco 94143 0450, USA
    Nature 398:436-41. 1999
    ..We propose that responses to noxious heat involve these related, but distinct, ion-channel subtypes that together detect a range of stimulus intensities...
  39. pmc Distribution of mRNA for vanilloid receptor subtype 1 (VR1), and VR1-like immunoreactivity, in the central nervous system of the rat and human
    E Mezey
    National Institutes of Health, National Institute of Neurological Disorders and Stroke, Basic Neuroscience Program, Bethesda, MD 20892, USA
    Proc Natl Acad Sci U S A 97:3655-60. 2000
    ..VRs in the brain (and putative endogenous vanilloids) may be involved in the control of emotions, learning, and satiety, just to name a few exciting possibilities...
  40. ncbi ATP-sensitive potassium currents in rat primary afferent neurons: biophysical, pharmacological properties, and alterations by painful nerve injury
    T Kawano
    Department of Anesthesiology, Anesthesia Research MEB, Medical College of Wisconsin, 8701 Watertown Plank Road, Milwaukee, WI 53226, USA
    Neuroscience 162:431-43. 2009
    ..Their biophysical and pharmacological properties are preserved even after axotomy, suggesting that K(ATP) channels in primary afferents remain available for therapeutic targeting against established neuropathic pain...
  41. ncbi Molecular mechanisms of neonatal hyperinsulinism
    Irina Giurgea
    INSERM U654 and Department of Genetics, Hopital Henri Mondor, Creteil, France
    Horm Res 66:289-96. 2006
    ..However, secondary causes of hyperinsulinism have to be considered such as fatty acid oxidation deficiency, congenital disorders of glycosylation and factitious hypoglycaemia secondary to Munchausen by proxy syndrome...
  42. ncbi Anandamide-induced neuroblastoma cell rounding via the CB1 cannabinoid receptors
    Isao Ishii
    Department of Molecular Genetics, National Institute of Neuroscience, NCNP, Ogawahigashi 4 1 1, Kodaira, Tokyo 187 8502, Japan
    Neuroreport 13:593-6. 2002
    ..These results suggest that the CB1 receptor could couple with G proteins that activate Rho (possibly G12/13) as well as Gi/o and Gs...
  43. ncbi Hyperinsulinism of infancy: novel ABCC8 and KCNJ11 mutations and evidence for additional locus heterogeneity
    Sharona Tornovsky
    Endocrinology and Metabolism Service, Hadassah Hebrew University Medical Center, Jerusalem 91120, Israel
    J Clin Endocrinol Metab 89:6224-34. 2004
    ..In four patients (27%), no mutations were identified. Thus, further genetic heterogeneity is suggested in this disorder. These patients represent a cohort that can be used for searching for mutations in other candidate genes...
  44. ncbi Assembly limits the pharmacological complexity of ATP-sensitive potassium channels
    Jonathan P Giblin
    Centre for Clinical Pharmacology, Department of Medicine, University College London, The Rayne Institute, London WC1E 6JJ, United Kingdom
    J Biol Chem 277:13717-23. 2002
    ..This incompatibility limits the pharmacological complexity of K(ATP) channels that may be observed in native tissues...
  45. pmc Ethanol modulates the VR-1 variant amiloride-insensitive salt taste receptor. II. Effect on chorda tympani salt responses
    Vijay Lyall
    Department of Physiology, Division of Nephrology, Virginia Commonwealth University, Richmond, VA 23298, USA
    J Gen Physiol 125:587-600. 2005
    ..VR-1 KO mice demonstrated no Bz-insensitive CT response to NaCl and no sensitivity to ethanol. We conclude that ethanol increases salt taste sensitivity by its direct action on the Bz-insensitive VR-1 variant salt taste receptor...
  46. pmc Hybrid assemblies of ATP-sensitive K+ channels determine their muscle-type-dependent biophysical and pharmacological properties
    Domenico Tricarico
    Department of Pharmacobiology, Faculty of Pharmacy, University of Bari, via Orabona no 4, 70120 Bari, Italy
    Proc Natl Acad Sci U S A 103:1118-23. 2006
    ..Muscle-specific K(ATP) subunit compositions contribute to the physiological performance of different muscle fiber types and determine the pharmacological actions of drugs modulating K(ATP) activity in muscle diseases...
  47. ncbi Molecular basis for species-specific sensitivity to "hot" chili peppers
    Sven Eric Jordt
    Department of Cellular and Molecular Pharmacology, University of California, San Francisco 94143, USA
    Cell 108:421-30. 2002
    ..Our findings provide a molecular basis for the ecological phenomenon of directed deterence and suggest that the capacity to detect capsaicin-like inflammatory substances is a recent acquisition of mammalian vanilloid receptors...
  48. ncbi Gitelman's syndrome: towards genotype-phenotype correlations?
    Eva Riveira-Munoz
    Pediatr Nephrol 22:326-32. 2007
    ....
  49. ncbi Morphological localisation of sulfonylurea receptor 1 in endocrine cells of human, mouse and rat pancreas
    Y Guiot
    Department of Pathology, Faculty of Medicine, University of Louvain, B 1200, Brussels, Belgium
    Diabetologia 50:1889-99. 2007
    ..Morphological methods (immunohistochemistry and sulfonylurea binding) were used to establish the cellular and subcellular location of SUR1 in human and rodent islets...
  50. ncbi cAMP-dependent protein kinase regulates desensitization of the capsaicin receptor (VR1) by direct phosphorylation
    Gautam Bhave
    Division of Neuroscience, Baylor College of Medicine, One Baylor Plaza, Houston, TX 77030, USA
    Neuron 35:721-31. 2002
    ..Given the significant roles of VR1 and PKA in inflammatory pain hypersensitivity, VR1 phosphorylation at Ser116 by PKA may represent an important molecular mechanism involved in the regulation of VR1 function after tissue injury...
  51. pmc Sulphonylurea receptor 2B and Kir6.1 form a sulphonylurea-sensitive but ATP-insensitive K+ channel
    M Yamada
    Department of Pharmacology II, Faculty of Medicine, Osaka University, Japan
    J Physiol 499:715-20. 1997
    ..5. Therefore, the K+ channel composed of SUR2B and Kir6.1 is not a classical ATP-sensitive K+ channel but closely resembles the nucleotide diphosphate-dependent K+ channel in vascular smooth muscle cells...
  52. ncbi Sulfonylurea stimulation of insulin secretion
    Peter Proks
    University Laboratory of Physiology, Oxford University, UK
    Diabetes 51:S368-76. 2002
    ..We also clarify the mechanism by which MgADP produces an apparent increase of sulfonylurea efficacy on channels containing SUR1 (but not SUR2)...
  53. ncbi Reconstitution of IKATP: an inward rectifier subunit plus the sulfonylurea receptor
    N Inagaki
    Division of Molecular Medicine, Chiba University School of Medicine, Japan
    Science 270:1166-70. 1995
    ..Gene mapping data show that these two potassium channel subunit genes are clustered on human chromosome 11 at position 11p15.1...
  54. pmc Clinical characteristics and biochemical mechanisms of congenital hyperinsulinism associated with dominant KATP channel mutations
    Sara E Pinney
    Division of Endocrinology Diabetes, The Children s Hospital of Philadelphia, Department of Genetics, University of Pennsylvania School of Medicine, Philadelphia, Pennsylvania 19104, USA
    J Clin Invest 118:2877-86. 2008
    ....
  55. pmc Voltage- and time-dependent properties of the recombinant rat vanilloid receptor (rVR1)
    M J Gunthorpe
    Neuroscience Research, SmithKline Beecham Pharmaceuticals, New Frontiers Science Park North, Harlow, Essex CM19 5AW, UK
    J Physiol 525:747-59. 2000
    ..Our data reveal that rVR1 exhibits substantial time- and voltage-dependent gating properties that may have significance for the physiology of sensory transduction of nociceptive signals...
  56. pmc Molecular identification and functional characterization of a mitochondrial sulfonylurea receptor 2 splice variant generated by intraexonic splicing
    Bin Ye
    Department of Medicine, University of Wisconsin, Madison, WI 53706, USA
    Circ Res 105:1083-93. 2009
    ..Cardioprotective pathways may involve a mitochondrial ATP-sensitive potassium (mitoK(ATP)) channel but its composition is not fully understood...
  57. ncbi Nicotine inhibits voltage-dependent sodium channels and sensitizes vanilloid receptors
    L Liu
    Department of Anesthesiology, Duke University, Durham 27710, USA
    J Neurophysiol 91:1482-91. 2004
    ..These studies document several new effects of nicotine on channels involved in nociception and indicate how they may impact physiological processes involving pain and gustation...
  58. ncbi Heart mitochondria contain functional ATP-dependent K+ channels
    Zsombor Lacza
    Department of Physiology and Pharmacology, Wake Forest University School of Medicine, Winston Salem, NC 27157, USA
    J Mol Cell Cardiol 35:1339-47. 2003
    ..We conclude that a functional K(ATP) channel is present in heart mitochondria, which can be opened by diazoxide or BMS-191095. The channel can be composed of Kir6.1 and Kir6.2 subunits and does not contain either SUR1 or SUR2...
  59. ncbi High-performance affinity beads for identifying anti-NF-kappa B drug receptors
    Masaki Hiramoto
    Department of Biological Information, Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Midori ku, Yokohama 226 8501, Japan
    Methods Enzymol 353:81-8. 2002
  60. pmc Structural determinant of TRPV1 desensitization interacts with calmodulin
    Mitsuko Numazaki
    Department of Cellular and Molecular Physiology, Mie University School of Medicine, Edobashi 2 174, Tsu, Mie 514 8507, Japan
    Proc Natl Acad Sci U S A 100:8002-6. 2003
    ..Compounds that interfere with the 35-aa segment could therefore prove useful in the treatment of pain...
  61. pmc Disruption of Sur2-containing K(ATP) channels enhances insulin-stimulated glucose uptake in skeletal muscle
    W A Chutkow
    Department of Medicine, University of Chicago, Chicago, IL 60637, USA
    Proc Natl Acad Sci U S A 98:11760-4. 2001
    ....
  62. pmc N-terminal transmembrane domain of the SUR controls trafficking and gating of Kir6 channel subunits
    Kim W Chan
    Department of Physiology and Biophysics, Mount Sinai School of Medicine, New York University, New York, NY 10029, USA
    EMBO J 22:3833-43. 2003
    ..2. These results underscore the importance of TMD0 in K(ATP) channel function, explaining how specific mutations within this domain result in disease, and suggest how an ABC protein has evolved to regulate a potassium channel...
  63. ncbi Physiological and pathophysiological roles of ATP-sensitive K+ channels
    Susumu Seino
    Department of Cellular and Molecular Medicine, Graduate School of Medicine, Chiba University, 1 8 1 Inohana Chuo ku, Chiba 260 8760, Japan
    Prog Biophys Mol Biol 81:133-76. 2003
    ..In this review, we focus on the physiological and pathophysiological roles of K(ATP) channels learned from genetic manipulation of mice and naturally occurring mutations in humans...
  64. pmc Insulin gene mutations as a cause of permanent neonatal diabetes
    Julie Støy
    Department of Medicine, University of Chicago, 5841 South Maryland Avenue, Chicago, IL 60637, USA
    Proc Natl Acad Sci U S A 104:15040-4. 2007
    ..One of the human mutations we report here is identical to that in the Akita mouse. The identification of insulin mutations as a cause of neonatal diabetes will facilitate the diagnosis and possibly, in time, treatment of this disorder...
  65. pmc Molecular basis of Kir6.2 mutations associated with neonatal diabetes or neonatal diabetes plus neurological features
    Peter Proks
    University Laboratory of Physiology, Oxford University, Oxford OX1 3PT, United Kingdom
    Proc Natl Acad Sci U S A 101:17539-44. 2004
    ..2 (V59G) influence the channel kinetics, providing evidence that this domain is involved in Kir channel gating, and suggest that the efficacy of sulfonylurea therapy in PNDM may vary with genotype...
  66. ncbi Update of mutations in the genes encoding the pancreatic beta-cell K(ATP) channel subunits Kir6.2 (KCNJ11) and sulfonylurea receptor 1 (ABCC8) in diabetes mellitus and hyperinsulinism
    Sarah E Flanagan
    Institute of Biomedical and Clinical Science, Peninsula Medical School, Exeter, United Kingdom
    Hum Mutat 30:170-80. 2009
    ..This review focuses on reported mutations in both genes, the spectrum of phenotypes, and the implications for treatment on diagnosing patients with mutations in these genes...
  67. ncbi A rare mutation in ABCC8/SUR1 leading to altered ATP-sensitive K+ channel activity and beta-cell glucose sensing is associated with type 2 diabetes in adults
    Andrei I Tarasov
    Section of Cell Biology, Division of Medicine, Imperial College London, London, UK
    Diabetes 57:1595-604. 2008
    ..We describe here an activating mutation in the ABCC8 gene, encoding SUR1, that is associated with the development of type 2 diabetes only in adults...
  68. ncbi The vanilloid receptor: a molecular gateway to the pain pathway
    M J Caterina
    Department of Biological Chemistry, Johns Hopkins University School of Medicine, Baltimore, Maryland 21205, USA
    Annu Rev Neurosci 24:487-517. 2001
    ..At the same time, these studies demonstrate the existence of redundant mechanisms for the sensation of heat-evoked pain...
  69. pmc Destabilization of ATP-sensitive potassium channel activity by novel KCNJ11 mutations identified in congenital hyperinsulinism
    Yu Wen Lin
    Center for Research on Occupational and Environmental Toxicology, Oregon Health and Science University, 3181 S W Sam Jackson Park Road, Portland, OR 97239, USA
    J Biol Chem 283:9146-56. 2008
    ..Our studies suggest the importance of Kir6.2 subunit-subunit interactions in K(ATP) channel gating and function and reveal a novel gating defect underlying CHI...
  70. ncbi Concurrent stimulation of cannabinoid CB1 and dopamine D2 receptors augments cAMP accumulation in striatal neurons: evidence for a Gs linkage to the CB1 receptor
    M Glass
    Laboratory of Cellular and Molecular Regulation, National Institute of Mental Health, Bethesda, Maryland 20892 4090, USA
    J Neurosci 17:5327-33. 1997
    ..Stimulation of cAMP accumulation was not observed after pertussis toxin treatment of CHO cells expressing the human CB2 receptor, suggesting that this novel signaling pathway is unique to the cannabinoid CB1 receptor...
  71. ncbi MgADP antagonism to Mg2+-independent ATP binding of the sulfonylurea receptor SUR1
    K Ueda
    Laboratory of Biochemistry, Division of Applied Life Sciences, Kyoto University Graduate School of Agriculture, Kyoto 606 01, Japan
    J Biol Chem 272:22983-6. 1997
    ..These results show that SUR1, unlike other ABC proteins, strongly binds ATP at NBF1 even in the absence of Mg2+ and that MgADP, through binding at NBF2, antagonizes the Mg2+-independent high affinity ATP binding at NBF1...
  72. ncbi Cloning of the promoters for the beta-cell ATP-sensitive K-channel subunits Kir6.2 and SUR1
    R Ashfield
    Nuffield Department of Clinical Biochemistry, John Radcliffe Hospital, Headington, Oxford, UK
    Diabetes 47:1274-80. 1998
    ..In contrast, over 900 bp of Kir6.2 5' sequence are required for similar high level expression, and deletion of the Alu repeat results in an increase in promoter activity...
  73. ncbi Association studies of variants in promoter and coding regions of beta-cell ATP-sensitive K-channel genes SUR1 and Kir6.2 with Type 2 diabetes mellitus (UKPDS 53)
    A L Gloyn
    Diabetes Research Laboratories, Nuffield Department of Clinical Medicine, University of Oxford, Radcliffe Infirmary, Oxford, UK
    Diabet Med 18:206-12. 2001
    ..Secondly, novel and previously described variants associated with Type 2 diabetes (SUR1 exon 16-3t, exon 18 T, and Kir6.2 E23K) were investigated in the UKPDS cohort...
  74. ncbi Clinical and molecular characterization of a dominant form of congenital hyperinsulinism caused by a mutation in the high-affinity sulfonylurea receptor
    Paul S Thornton
    Children s Hospital of Philadelphia, Philadelphia, Pennsylvania 19104, USA
    Diabetes 52:2403-10. 2003
    ..2 and trafficks to the plasma membrane, but it had no (86)Rb efflux ion transport activity. These results indicate that hyperinsulinism in this family is caused by a SUR1 mutation that is expressed dominantly rather than recessively...
  75. ncbi Hyperinsulinism in mice with heterozygous loss of K(ATP) channels
    M S Remedi
    Department of Cell Biology and Physiology, Washington University School of Medicine, 660 South Euclid Avenue, St Louis, MO 63110, USA
    Diabetologia 49:2368-78. 2006
    ..Thus, we propose that partial loss of beta cell K(ATP) in vivo causes insulin hypersecretion, but complete absence may cause insulin secretory failure...
  76. ncbi Hyperinsulinism caused by paternal-specific inheritance of a recessive mutation in the sulfonylurea-receptor gene
    B Glaser
    Department of Endocrinology and Metabolism, Hebrew University, Hadassah Medical School, Jerusalem, Israel
    Diabetes 48:1652-7. 1999
    ..001). In conclusion, we identified a novel mechanism to explain the pathophysiology of focal HI and provide evidence to suggest that this entity may be self-limiting, since affected beta-cells undergo apoptosis...
  77. ncbi Conserved mechanisms of glucose sensing and regulation by Drosophila corpora cardiaca cells
    Seung K Kim
    Department of Developmental Biology, Stanford University School of Medicine, Beckman Center B300, Stanford, California 94305 5329, USA
    Nature 431:316-20. 2004
    ..Thus, Drosophila CC cells are crucial regulators of glucose homeostasis and they use glucose-sensing and response mechanisms similar to islet cells...
  78. pmc Analysis of the differential modulation of sulphonylurea block of beta-cell and cardiac ATP-sensitive K+ (K(ATP)) channels by Mg-nucleotides
    Frank Reimann
    University Laboratory of Physiology, Parks Road, Oxford OX1 3PT, UK
    J Physiol 547:159-68. 2003
    ....
  79. ncbi Pathophysiology of functional mutations of the thiazide-sensitive Na-Cl cotransporter in Gitelman disease
    Ernesto Sabath
    Molecular Physiology Unit, Instituto Nacional de Ciencias Medicas y Nutricion Salvador Zubiran, Instituto de Investigaciones Biomedicas, Universidad Nacional Autonoma de Mexico, Tlalpan 14000, Mexico City, Mexico
    Am J Physiol Renal Physiol 287:F195-203. 2004
    ..The small increase in Cl(-) and thiazide affinity in G610S and G627V suggests that the beginning of the COOH-terminal domain could be implicated in defining kinetic properties...
  80. ncbi Potent and selective activation of the pancreatic beta-cell type K(ATP) channel by two novel diazoxide analogues
    M Dabrowski
    University Laboratory of Physiology, Parks Road, Oxford, UK
    Diabetologia 46:1375-82. 2003
    ..2/SUR2A), smooth muscle (Kir6.2/SUR2B) and pancreatic beta cell (Kir6.2/SUR1) types of K(ATP) channel...
  81. ncbi Pharmacological modulation of K(ATP) channels
    F M Gribble
    Department of Clinical Biochemistry, Addenbrooke s Hospital, Cambridge CB2 2QR, U K
    Biochem Soc Trans 30:333-9. 2002
    ..In this review, we discuss the molecular basis of tissue-specific drug action, and its implications for clinical practice...
  82. ncbi ABCC8 (SUR1) and KCNJ11 (KIR6.2) mutations in persistent hyperinsulinemic hypoglycemia of infancy and evaluation of different therapeutic measures
    Feyza Darendeliler
    Department of Pediatrics, Istanbul Faculty of Medicine, Istanbul University, Turkey
    J Pediatr Endocrinol Metab 15:993-1000. 2002
    ..Unidentified mutations in the K+ATP channels other than those screened or other functional abnormalities in these channels may account for the different therapeutic responses...
  83. pmc Capsaicin activation of the pain receptor, VR1: multiple open states from both partial and full binding
    Kwokyin Hui
    Department of Physiology and Biophysical Sciences, State University of New York at Buffalo, 14214, USA
    Biophys J 84:2957-68. 2003
    ....
  84. pmc Potassium channel regulation
    Jeff D Campbell
    University Laboratory of Physiology, Parks Road, Oxford OX1 3PT, UK
    EMBO Rep 4:1038-42. 2003
    ..We discuss the experimental data in the context of this model, and show how the model can be used to design experiments aimed at elucidating the relationship between the structure and function of the KATP channel...
  85. ncbi Large-scale association studies of variants in genes encoding the pancreatic beta-cell KATP channel subunits Kir6.2 (KCNJ11) and SUR1 (ABCC8) confirm that the KCNJ11 E23K variant is associated with type 2 diabetes
    Anna L Gloyn
    Centre for Molecular Genetics, Peninsula Medical School, Exeter, UK
    Diabetes 52:568-72. 2003
    ..000002); but the ABCC8 variants were not associated. Our results confirm that E23K increases risk of type 2 diabetes and show that large-scale association studies are important for the identification of diabetes susceptibility alleles...
  86. pmc Subunit modification and association in VR1 ion channels
    Tamara Rosenbaum
    Department of Ophthalmology, Department of Physiology and Biophysics, University of Washington, Box 356485, Seattle, WA 98195 6485, USA
    BMC Neurosci 3:4. 2002
    ..The capsaicin (vanilloid) receptor, VR1, is an agonist-activated ion channel expressed by sensory neurons that serves as a detector of chemical and thermal noxious stimuli...
  87. pmc The N-terminal transmembrane domain (TMD0) and a cytosolic linker (L0) of sulphonylurea receptor define the unique intrinsic gating of KATP channels
    Kun Fang
    Department of Physiology and Biophysics, School of Medicine, Case Western Reserve University, Cleveland, OH 44106 4970, USA
    J Physiol 576:379-89. 2006
    ..2. However, TMD0 and L0 are responsible for the different gating patterns of full-length SUR1 and SUR2A channels. A kinetic model with one open and four closed states is presented to explain our results in a mechanistic context...
  88. ncbi Transcriptional and functional analyses of SLC12A3 mutations: new clues for the pathogenesis of Gitelman syndrome
    Eva Riveira-Munoz
    Division of Nephrology, Université Catholique de Louvain Medical School, Brussels, Belgium
    J Am Soc Nephrol 18:1271-83. 2007
    ..These data suggest that the nature/position of SLC12A3 mutation, combined with male gender, is a determinant factor in the severity of GS and provide new insights in the underlying pathogenic mechanisms of the disease...
  89. ncbi Sur1 knockout mice. A model for K(ATP) channel-independent regulation of insulin secretion
    V Seghers
    Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    J Biol Chem 275:9270-7. 2000
    ....
  90. ncbi Testing the bipartite model of the sulfonylurea receptor binding site: binding of A-, B-, and A + B-site ligands
    Marcus Winkler
    Department of Pharmacology and Toxicology, Medical Faculty, University of Tubingen, Wilhelmstrasse 56, D 72074 Tubingen, Germany
    J Pharmacol Exp Ther 322:701-8. 2007
    ..The affinity of B-ligands is altered by the mutation SUR2(Y1206S), suggesting that the mutation affects the binding chamber of SUR2 as a whole or subsite A, including the region where the subsites overlap...
  91. ncbi Pharmaco-topology of sulfonylurea receptors. Separate domains of the regulatory subunits of K(ATP) channel isoforms are required for selective interaction with K(+) channel openers
    A P Babenko
    Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas 77030, USA
    J Biol Chem 275:717-20. 2000
    ..These data are incorporated into a functional topology model for the regulatory SUR subunits of K(ATP) channels...
  92. pmc Involvement of the n-terminus of Kir6.2 in coupling to the sulphonylurea receptor
    F Reimann
    University Laboratory of Physiology, Parks Road, Oxford OX1 3PT, UK
    J Physiol 518:325-36. 1999
    ..8 and are not blocked by tolbutamide). Thus the N-terminus of Kir6.2 may be involved in coupling sulphonylurea binding to SUR1 to closure of the Kir6.2 pore...
  93. pmc Glucose-receptive neurones in the rat ventromedial hypothalamus express KATP channels composed of Kir6.1 and SUR1 subunits
    K Lee
    Parke Davis Neuroscience Research Centre, Cambridge University Forvie Site, Cambridge CB2 2QB, UK
    J Physiol 515:439-52. 1999
    ..2 or SUR2. 6. It is concluded that glucose-receptive neurones within the rat ventromedial hypothalamus exhibit a KATP channel current with pharmacological and molecular properties similar to those reported in other tissues...
  94. pmc K(ATP) channel pharmacogenomics: from bench to bedside
    S Sattiraju
    Marriott Heart Disease Research Program, Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic, Rochester, Minnesota, USA
    Clin Pharmacol Ther 83:354-7. 2008
    ..There is an increased recognition that genetic variability of the K(ATP) channel impacts therapeutic decision-making in human disease...
  95. ncbi Capsaicin sensitivity is associated with the expression of the vanilloid (capsaicin) receptor (VR1) mRNA in adult rat sensory ganglia
    R J Helliwell
    Novartis Institute for Medical Sciences, London, UK
    Neurosci Lett 250:177-80. 1998
    ....
  96. ncbi Subjects heterozygous for genetic loss of function of the thiazide-sensitive cotransporter have reduced blood pressure
    C Fava
    Department of Clinical Sciences, Lund University, Malmo, Sweden
    Hum Mol Genet 17:413-8. 2008
    ....
  97. pmc Functional clustering of mutations in the dimer interface of the nucleotide binding folds of the sulfonylurea receptor
    Ricard Masia
    Department of Cell Biology and Physiology, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Biol Chem 283:30322-9. 2008
    ..Overall, the data support the idea that SUR1 NBFs assemble as heterodimers and that this interaction is functionally critical...
  98. pmc Association of the Kir6.2 E23K variant with reduced acute insulin response in African-Americans
    Nicholette D Palmer
    Department of Biochemistry, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, USA
    J Clin Endocrinol Metab 93:4979-83. 2008
    ..2 and SUR1 are expressed in a broad range of tissues, and no contemporary studies have addressed the physiological impact of variants in Hispanic-Americans and African-Americans carefully phenotyped for components of glucose homeostasis...
  99. pmc Overexpression of SUR2A generates a cardiac phenotype resistant to ischemia
    Qingyou Du
    Maternal and Child Health Sciences, Ninewells Hospital and Medical School, University of Dundee, Dundee, DD1 9SY Scotland, UK
    FASEB J 20:1131-41. 2006
    ..We conclude that overexpression of SUR2A generates cardiac phenotype resistant to hypoxia/ischemia/reperfusion injury due at least in part to increase in levels of sarcolemmal K(ATP) channels...
  100. ncbi Intracellular ATP-sensitive K+ channels in mouse pancreatic beta cells: against a role in organelle cation homeostasis
    A Varadi
    Henry Wellcome Laboratories for Integrated Cell Signalling and Department of Biochemistry, School of Medical Sciences, University of Bristol, University Walk, Bristol, BS8 1TD, UK
    Diabetologia 49:1567-77. 2006
    ..The aim of this study was to explore these possibilities and to test the hypothesis that vesicle-resident channels play a role in the control of organellar Ca(2+) concentration or pH...
  101. pmc ATP-sensitive K+ channel channel/enzyme multimer: metabolic gating in the heart
    Alexey E Alekseev
    Division of Cardiovascular Diseases, Department of Medicine, Mayo Clinic College of Medicine, Rochester, MN 55905, USA
    J Mol Cell Cardiol 38:895-905. 2005
    ....

Research Grants62

  1. General Anesthetic Sites in GABA-A Receptor Subunit Interfacial Pockets
    Stuart A Forman; Fiscal Year: 2013
    ....
  2. Local anesthetic receptor in peripheral Na+ channels
    GING K WANG; Fiscal Year: 2013
    ..Our goals are to delimit such a receptor in peripheral Nav1.7 and Nav1.8 channels, to resolve the drug/receptor interactions during state transitions, and to explore this receptor site for novel pain therapeutics. ..
  3. Training Program in Pharmaceutical Sciences
    Robert S Kass; Fiscal Year: 2012
    ....
  4. Does Anesthetic Solubility Determine Receptor Specificity?
    ROBERT JOSEPH BROSNAN; Fiscal Year: 2013
    ..The role of water solubility as a determinant of drug-receptor modulation would also add additional support to theories of anesthetic action at aqueous interfacial sites around cell receptor proteins. ..
  5. Expression Genetics in Drug Therapy
    Wolfgang Sadee; Fiscal Year: 2013
    ..In addition, building on other ongoing studies, the project includes genes encoding drug receptors/targets, with focus on CNS disorders (schizophrenia) and cardiovascular diseases (myocardial infarction, lipid ..
  6. PROBING RECEPTOR STRUCTURES WITH UNNATURAL AMINO ACIDS
    Dennis A Dougherty; Fiscal Year: 2010
    ..When combined with the power of electrophysiology, unnatural amino acid mutagenesis becomes a powerful, broadly applicable tool for unraveling the critical features of these central players in molecular neurobiology. ..
  7. Benzodiazepine Analogs as Novel Treatments for Catatonia
    HOWARD P SARD; Fiscal Year: 2012
    ..The long- term goal of this project is to discover a new, improved pharmaceutical agent for treatment of catatonia that can be licensed and developed for ultimate market approval. ..
  8. Preclinical Evaluation of GluR2-3Y Peptide as a Potential New Medication for Poly
    Yu Tian Wang; Fiscal Year: 2013
    ..This peptide compound does not directly target drug receptors, but rather targets the association and learning mechanisms underlying addiction behaviors...
  9. Heterocycle Cation Recognition of the DNA Minor Groove.
    W David Wilson; Fiscal Year: 2013
    ..It is, therefore, essential to identify other drug receptors such as DNA, particularly DNA structures that allow selective targeting...
  10. Synthesis and Study of Minimal Protein Folding Models: Molecular Torsion Balance
    Craig S Wilcox; Fiscal Year: 2010
    ..Knowledge gained in these experimental studies will be available for testing current computational methods and theories of biological recognition and in identifying guiding principles for design of biologically active agents. ..
  11. Mechanistic studies of the GYKI Compounds
    Li Niu; Fiscal Year: 2013
    ..These compounds are candidates for developing potential drugs to treat a number of neurological diseases involving AMPA receptors. ..
  12. Membrane Protein Structures in Phospholipid Bilayers by Solid State NMR
    STANLEY OPELLA; Fiscal Year: 2009
    ..are responsible for many essential biological functions, including as the largest and most important class of drug receptors. More than 20% of the proteins encoded in the human genome are helical membrane proteins, and many human ..
  13. Impact of Pharmacology on Duration of Ventilation in Patients with Resp Failure
    Athena F Zuppa; Fiscal Year: 2012
    ..g. polymorphisms in drug metabolizing systems or drug receptors) factors that can be quantitatively defined...
  14. Predictive QSAR Modeling of HIV-1 Integrase Inhibitors
    Rajni Garg; Fiscal Year: 2009
    ..The goal of this project is to understand the interactions between the HIV-1 integrase enzyme and its inhibitors that will help in the design of new drugs active against drug-resistant HIV-1. ..
  15. Computational methods for NMR structure determination of proteins in membranes
    Francesca M Marassi; Fiscal Year: 2011
    ..Membrane proteins are the principal class of drug receptors and this research will accelerate the discovery of drugs for many diseases.
  16. OPIOID RECEPTOR CONSTANTS IN VITRO--TEMPERATURE
    Frank Porreca; Fiscal Year: 1990
    ..Knowledge of these fundamental opioid parameters should be instrumental in the process of rational drug design, particularly for antagonists...
  17. PHARMACOGENETICS AND RESPONSE TO THERAPY IN OLDER ADULTS
    SUSAN HECKBERT; Fiscal Year: 2000
    The goal of this research is to investigate whether genetic polymorphisms in drug metabolizing enzymes, drug receptors, and drug effector pathways explain some of the variability in response to drug therapy for common conditions in older ..
  18. ADRENERGIC & CHOLINERGIC MECHANISMS IN GLAUCOMA THERAPY
    JON POLANSKY; Fiscal Year: 1993
    ..g. beta adrenergic drug receptors and responses have been examined in HIM tissue, and cholinergic drug actions have been assessed in isolated ..
  19. STRUCTURAL INVESTIGATIONS OF MODE OF ACTION OF DRUGS
    Satish Arora; Fiscal Year: 1991
    ..Also, modifications to the structures of the drugs can be postulated to enhance their therapeutic selectivity...
  20. ANTIHYPERTENSIVE DRUG/GENE INTERACTIONS AND CV EVENTS
    Bruce Psaty; Fiscal Year: 2004
    Over the centuries, large numbers of polymorphisms in drug receptors, drug effector pathways, and other proteins developed. Some variant alleles have prospered in the absence of exposures to modern medications...
  21. PHARMACOLOGY OF A GAMMA-AMINOBUTRIC ACID RECEPTOR
    JOEL GALLAGHER; Fiscal Year: 1980
    ....
  22. DRUG EFFECTS ON ELECTRICALLY EXCITABLE MEMBRANES
    EDWARD GROOD; Fiscal Year: 1980
    ..Transition from closed to open for drug-bound channels are determined by different voltage and time dependencies. Additional drug-receptor binding is either also voltage-dependent or depends on the confirmation of the channel. ..
  23. MEMBRANE-BOUND ENZYMES AND DRUG RECEPTORS IN MUSCLE
    Thomas Mittag; Fiscal Year: 1980
    ..The relationship of protein kinase activity and phosphorylated membrane state to calcium binding by sarcolemma will also be studied...
  24. SELECTIVE ACTIVATION OF DOPAMINE RECEPTOR SUBPOPULATIONS
    Richard Mailman; Fiscal Year: 2001
    ..Agonist-induced binding of [alpha-32P]GTP to G-proteins isoforms in striatal membranes and MN9D cells will be used as a marker of G-protein activation. ..
  25. SELECTIVE ACTIVATION OF DOPAMINE RECEPTOR SUBPOPULATIONS
    Cindy Lawler; Fiscal Year: 1999
    ..Agonist-induced binding of [alpha-32P]GTP to G-proteins isoforms in striatal membranes and MN9D cells will be used as a marker of G-protein activation. ..
  26. NEONATAL THERAPEUTIC CAFFEINE AND NEURAL DEVELOPMENT
    Ronnie Guillet; Fiscal Year: 1990
    ..These studies will provide information on neural developmental implications for human premature neonates of chronic exposure to therapeutic levels of caffeine...
  27. ROLE OF SIGMA RECEPTORS IN MOVEMENT DISORDERS
    Wayne Bowen; Fiscal Year: 1991
    ..The possibility that sigma receptors are involved in motor function and dysfunction suggests that sigma ligands may potentially be useful in treatment of some motor disorders...
  28. 2009 Molecular Pharmacology Gordon Research Conference
    Paul Insel; Fiscal Year: 2009
    ..translational, by highlighting recent advances in molecular mechanisms and pathophysiological implications of drug receptors and drug action through the use of experimental and clinically relevant models...
  29. Structure of Mammary Tumor Mat8 and the FXYD proteins
    Francesca Marassi; Fiscal Year: 2005
    ..and of the other FXYD proteins, provide the initial insight into their mechanisms of action and potential as a drug receptors: since inhibitors of the Mat8 channel may kill breast cancer cells, this protein is an attractive candidate ..
  30. BEHAVIORAL PHARMACOLOGY OF NARCOTIC ANTAGONISTS
    STEPHEN HOLTZMAN; Fiscal Year: 2002
    ..Acute agonist-induced sensitization to opioid antagonists appears to be an exquisite example of neuronal plasticity, reflecting the first hours of the drug-receptor interactions that lead to chronic physical dependence upon opioids. ..
  31. PK-PD Models: The Role of Metabolites in Drug Action
    Howard Hendrickson; Fiscal Year: 2004
    ..This approach should provide evidence about whether dextromethorphan or dextrorphan, or both, are primarily responsible for the actions sought by abusers. ..
  32. MOLECULAR POLYPHARMACY: Modulation of GABAA Receptors
    JAMES CELENTANO; Fiscal Year: 2001
    Many drug receptors are allosteric proteins and efficacy reflects the extent to which agents cause structural changes. The long term goal of this study is to understand the molecular nature of drug efficacy...
  33. METHODOLOGY DEVELOPMENT FOR NMR STUDIES OF BIOMOLECULES
    Mark Rance; Fiscal Year: 2003
    ..The correct interpretation of NMR data depends critically on having a detailed understanding of the underlying spin physics of the experiments. ..
  34. NOVEL MOLECULAR SITE FOR ANTIDOPAMINERGIC ACTION
    Richard Mailman; Fiscal Year: 2001
    ..These studies will not only be useful for heuristic reasons, but may affect the pending use of D1 agonists in several clinical conditions. ..
  35. MOLECULAR MECHANISMS OF CANNABINOID RECEPTOR REGULATION
    Mary Abood; Fiscal Year: 2006
    ..The consequences of CB1 receptor mutation may be altered neurological functions including predisposition to addiction. ..
  36. BIACORE 3000
    Clayton Naeve; Fiscal Year: 2000
    ..The instrument will be incorporated into the Center for Biotechnology at St. Jude Children's Research Hospital. ..
  37. VORONOI MAPPING OF COCAINE RECEPTORS
    Gordon Crippen; Fiscal Year: 1992
    ....
  38. CHARACTERIZATION OF A NOVEL BENZODIAZEPINE BINDING SITE
    KELVIN GEE; Fiscal Year: 1992
    ....
  39. Reactive astrocytes from gliotic capsule
    J Marc Simard; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  40. CEREBROVASCULAR ION CHANNELS IN HYPERTENSION
    J Marc Simard; Fiscal Year: 2007
    ..abstract_text> ..
  41. PATHOPHYSIOLOGY OF NICOTINE IN CEREBRAL BLOOD VESSELS
    J Simard; Fiscal Year: 2004
    ....
  42. Determinants of alpha1-adrenoceptor affinity & efficacy
    Dan McCune; Fiscal Year: 2004
    ..Drugs with improved selectivity will be beneficial for the clinical treatment of alpha1-AR-related cardiovascular diseases. ..
  43. Synthesis of Cannabinoid Receptor Ligands
    John Huffman; Fiscal Year: 2005
    ..A number of new classical cannabinoids will be synthesized, including additional 1',2'-dimethylheptyl-delta8-tetrahydrocannabinol analogues and the six geminally disubstituted dimethylheptyl-delta8-tetrahydrocannabinols. ..
  44. SYNTHESIS OF CANNABINOIDS, ANALOGUES AND METABOLITES
    John Huffman; Fiscal Year: 2009
    ..There a possibility that these metabolites may be contributing to the enhanced potency of cannabinoids with a dimethylheptyl side chain. ..
  45. MOTOR ACTIONS OF CANNABINOIDS IN A PARKINSONS MODEL
    CLARA SANUDO PENA; Fiscal Year: 2002
    ..Behavioral, biochemical, and physiological studies will be conducted in parallel to test this possibility. It will also help integrate the cannabinergic system with the current knowledge of basal ganglia physiology. ..
  46. PET Studies of Alcohol Distribution and Metabolism
    Andrew Gifford; Fiscal Year: 2005
    ..abstract_text> ..
  47. Structure and Function of CB2 Cannabinoid Receptor
    Zhao Hui Song; Fiscal Year: 2008
    ..The drugs that specifically targeted at CB2 should be devoid of psvchoactive side effects of marijuana. ..
  48. Cannabinoid Receptors and Novel Antiglaucoma Drugs
    Zhao Hui Song; Fiscal Year: 2010
    ..These studies should also contribute to our understanding of the homeostasis of aqueous humor outflow and may lead to the development of better therapeutic agents for lowering IOP. ..
  49. Animal model for inhalant abuse
    Andrew Gifford; Fiscal Year: 2004
    ..Additionally, an animal model for inhalant abuse will aid further exploration of the factors contributing to the predisposition, development and potential treatment of inhalant abuse. ..
  50. MODULATION OF NEUROTRANSMITTER RELEASE BY CANNABINOIDS
    Andrew Gifford; Fiscal Year: 2002
    ..Furthermore, these experiments will give information on the mode of action of cannabinoid antagonists and could suggest novel therapeutic uses for this new class of compounds. ..
  51. PERIPHERAL SOMATOSTATIN CONTROLS INFLAMMATORY PAIN
    Susan Carlton; Fiscal Year: 2004
    ..Peripheral SST receptors offer novel targets for nociceptor modulation and are likely targets for further development of non-opioid therapies to aid in reducing the pain and long-term deleterious changes that can accompany inflammation. ..
  52. Endogenous Activators of Vanilloid Receptor
    LOUIS PREMKUMAR; Fiscal Year: 2004
    ..In this way a range of normally benign stimuli will become potent activators of VRs. This research has important implications for understanding the role of VRs in hyperalgesia, chronic pain and other non-sensory functions. ..
  53. Molecular Pain Mechanisms
    Gerard P Ahern; Fiscal Year: 2010
    ..In Aim 3 we plan to identify nociceptive behaviors and pathology arising from cationic regulation of TRPV1. ..
  54. Brain Endocannabinoids and Chronic Stress
    Cecilia Hillard; Fiscal Year: 2005
    ..The successful completion of these studies will enhance our understanding of the processes involved in the adaptation of the brain to chronic stress. ..
  55. Role of Vanilloid Receptors in Diabetic Peripheral Neuropathy
    LOUIS PREMKUMAR; Fiscal Year: 2008
    ..The complications of DPN can be prevented/delayed by maintaining normal glucose levels and expression and function of TRP channels by therapeutic interventions. ..
  56. Calcium Signaling in Dendritic Cell Function
    Gerard Ahern; Fiscal Year: 2006
    ..Aim 2 tests the impact of endogenous and pharmacologic activators of RyR1 on DC. In Aim 3, we will elucidate the role of calcium-triggered secretion in DC. ..
  57. ENDOCANNABINOIDS AND VOLUNTARY ETHANOL CONSUMPTION
    Basalingappa Hungund; Fiscal Year: 2008
    ..abstract_text> ..
  58. Non-Peptide Somatostatin Agonist Analgesics
    Susan Carlton; Fiscal Year: 2007
    ..unreadable] [unreadable] [unreadable]..
  59. CANNABINOIDERGIC CONTROL OF ALCOHOL RELATED BEHAVIORS
    Basalingappa Hungund; Fiscal Year: 2006
    ..Studies with synthetic analogues of ANA or other agonists and antagonists will open up new avenues in alcohol research. ..
  60. Cannabinoid Receptors and Cerebrovascular Function
    Cecilia Hillard; Fiscal Year: 2006
    ..Increased understanding of the mediators that are released by activated microglia and their targets may provide new therapeutic approaches to CNS diseases with an inflammatory component. ..