Muscarinic acetylcholine receptors: mutant mice provide new insights for drug development

Muscarinic acetylcholine receptors (mAChRs), M1–M5, regulate the activity of numerous fundamental central and peripheral functions. The lack of small-molecule ligands that can block or activate specific mAChR subtypes with high selectivity has remained a major obstacle in defining the roles of the individual receptor subtypes and in the development of novel muscarinic drugs. Recently, phenotypic analysis of mutant mouse strains deficient in each of the five mAChR subtypes has led to a wealth of new information regarding the physiological roles of the individual receptor subtypes. 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.

[1]  W. Stigelman,et al.  Goodman and Gilman's the Pharmacological Basis of Therapeutics , 1986 .

[2]  W. Messer.  Cholinergic agonists and the treatment of Alzheimer's disease. , 2002, Current topics in medicinal chemistry.

[3]  T. Manabe,et al.  Mice Lacking M2 and M3 Muscarinic Acetylcholine Receptors Are Devoid of Cholinergic Smooth Muscle Contractions But Still Viable , 2002, The Journal of Neuroscience.

[4]  A. Levey,et al.  Muscarinic acetylcholine receptor subtypes in cerebral cortex and hippocampus. , 2004, Progress in brain research.

[5]  F. Bymaster,et al.  Muscarinic receptors as a target for drugs treating schizophrenia. , 2002, Current drug targets. CNS and neurological disorders.

[6]  J. Wess,et al.  Cholinergic stimulation of salivary secretion studied with M1 and M3 muscarinic receptor single- and double-knockout mice. , 2004, Molecular pharmacology.

[7]  B. K. Hartman,et al.  Distribution of pontomesencephalic cholinergic neurons projecting to substantia nigra differs significantly from those projecting to ventral tegmental area , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[8]  R. Quirion,et al.  Antisense oligodeoxynucleotides against the muscarinic m2, but not m4, receptor supports its role as autoreceptors in the rat hippocampus. , 1999, Brain research. Molecular brain research.

[9]  R. Eglen.  Muscarinic receptor subtypes in neuronal and non-neuronal cholinergic function. , 2006, Autonomic & autacoid pharmacology.

[10]  J. Wess,et al.  M2 and M3 muscarinic receptor‐mediated contractions in longitudinal smooth muscle of the ileum studied with receptor knockout mice , 2005 .

[11]  F. LaFerla,et al.  M1 Receptors Play a Central Role in Modulating AD-like Pathology in Transgenic Mice , 2006, Neuron.

[12]  J. Wess,et al.  Characterization of Central Inhibitory Muscarinic Autoreceptors by the Use of Muscarinic Acetylcholine Receptor Knock-Out Mice , 2002, The Journal of Neuroscience.

[13]  J. Wess,et al.  M3 receptor knockout mice: Muscarinic receptor function in atria, stomach fundus, urinary bladder and trachea in vitro , 2002 .

[14]  Y. Komiya,et al.  Multiple functional defects in peripheral autonomic organs in mice lacking muscarinic acetylcholine receptor gene for the M3 subtype. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[15]  R. Quirion,et al.  Alzheimer’s disease and the basal forebrain cholinergic system: relations to β-amyloid peptides, cognition, and treatment strategies , 2002, Progress in Neurobiology.

[16]  J. Yeomans,et al.  M5 Muscarinic Receptors Are Required for Prolonged Accumbal Dopamine Release after Electrical Stimulation of the Pons in Mice , 2002, The Journal of Neuroscience.

[17]  P. Jeffrey Conn,et al.  N-desmethylclozapine, an allosteric agonist at muscarinic 1 receptor, potentiates N-methyl-d-aspartate receptor activity , 2003, Proceedings of the National Academy of Sciences of the United States of America.

[18]  C. Bogardus,et al.  CHRM3 Gene Variation Is Associated With Decreased Acute Insulin Secretion and Increased Risk for Early-Onset Type 2 Diabetes in Pima Indians , 2006, Diabetes.

[19]  T. Manabe,et al.  Modulation of Synaptic Plasticity by Physiological Activation of M1 Muscarinic Acetylcholine Receptors in the Mouse Hippocampus , 2005, The Journal of Neuroscience.

[20]  M. Meaney,et al.  Long-term effects of BIBN-99, a selective muscarinic M2 receptor antagonist, on improving spatial memory performance in aged cognitively impaired rats , 2003, Behavioural Brain Research.

[21]  S. Kahn,et al.  The Importance of β-Cell Failure in the Development and Progression of Type 2 Diabetes , 2001 .

[22]  A. Niijima,et al.  Neural mechanisms in the control of blood glucose concentration. , 1989, The Journal of nutrition.

[23]  F. Bymaster,et al.  Towards a muscarinic hypothesis of schizophrenia , 2007, Molecular Psychiatry.

[24]  Carolina Roza,et al.  Muscarinic M2 Receptors on Peripheral Nerve Endings: A Molecular Target of Antinociception , 2002, The Journal of Neuroscience.

[25]  J. Wess,et al.  Muscarinic acetylcholine receptor knockout mice: novel phenotypes and clinical implications. , 2004, Annual review of pharmacology and toxicology.

[26]  B. AhrØn,et al.  Autonomic regulation of islet hormone secretion ± Implications for health and disease , 2000 .

[27]  A. Levey,et al.  Disruption of the m1 receptor gene ablates muscarinic receptor-dependent M current regulation and seizure activity in mice. , 1997, Proceedings of the National Academy of Sciences of the United States of America.

[28]  A. Levey,et al.  Differential expression of D1 and D2 dopamine and m4 muscarinic acetylcholine receptor proteins in identified striatonigral neurons , 1997, Synapse.

[29]  J. Wess,et al.  Novel signaling pathways mediating reciprocal control of keratinocyte migration and wound epithelialization through M3 and M4 muscarinic receptors , 2004, The Journal of cell biology.

[30]  J. Wess,et al.  Thromboxane A2 induces airway constriction through an M3 muscarinic acetylcholine receptor-dependent mechanism. , 2006, American journal of physiology. Lung cellular and molecular physiology.

[31]  J. Wess,et al.  M4 muscarinic receptors regulate the dynamics of cholinergic and dopaminergic neurotransmission: relevance to the pathophysiology and treatment of related central nervous system pathologies , 2004, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[32]  R. Eglen,et al.  Muscarinic receptor subtypes and smooth muscle function. , 1996, Pharmacological reviews.

[33]  Alcino J. Silva,et al.  Selective cognitive dysfunction in acetylcholine M1 muscarinic receptor mutant mice , 2003, Nature Neuroscience.

[34]  J. Wess,et al.  Enhancement of D1 dopamine receptor-mediated locomotor stimulation in M(4) muscarinic acetylcholine receptor knockout mice. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[35]  E. T. Iwamoto,et al.  Characterization of the antinociception produced by intrathecally administered muscarinic agonists in rats. , 1993, The Journal of pharmacology and experimental therapeutics.

[36]  M. Matsui,et al.  Effects of muscarinic receptor type 3 knockout on mouse islet secretory responses. , 2004, Biochemical and biophysical research communications.

[37]  P. Stengel,et al.  Muscarinic receptor knockout mice: role of muscarinic acetylcholine receptors M(2), M(3), and M(4) in carbamylcholine-induced gallbladder contractility. , 2002, The Journal of pharmacology and experimental therapeutics.

[38]  J. Wess,et al.  Loss of vagally mediated bradycardia and bronchoconstriction in mice lacking M2 or M3 muscarinic acetylcholine receptors , 2004, FASEB journal : official publication of the Federation of American Societies for Experimental Biology.

[39]  R. Wise,et al.  The neurobiology of addiction , 2019, Annals of the New York Academy of Sciences.

[40]  J. Yeomans,et al.  Decreased Amphetamine-Induced Locomotion and Improved Latent Inhibition in Mice Mutant for the M5 Muscarinic Receptor Gene Found in the Human 15q Schizophrenia Region , 2004, Neuropsychopharmacology.

[41]  A. Levey,et al.  Activation of the genetically defined m1 muscarinic receptor potentiates N-methyl-D-aspartate (NMDA) receptor currents in hippocampal pyramidal cells. , 1998, Proceedings of the National Academy of Sciences of the United States of America.

[42]  J. Growdon,et al.  Current pharmacotherapy for Alzheimer's disease. , 2006, Annual review of medicine.

[43]  P. Gilon,et al.  Mechanisms and physiological significance of the cholinergic control of pancreatic beta-cell function. , 2001, Endocrine reviews.

[44]  E. Mulugeta,et al.  Snake toxins with high selectivity for subtypes of muscarinic acetylcholine receptors. , 2000, Biochimie.

[45]  K. Mikoshiba,et al.  M3 muscarinic acetylcholine receptor plays a critical role in parasympathetic control of salivation in mice , 2004, The Journal of physiology.

[46]  F. Bymaster,et al.  Therapeutic Opportunities for Muscarinic Receptors in the Central Nervous System , 2001 .

[47]  Micaela Morelli,et al.  Modulatory functions of neurotransmitters in the striatum: ACh/dopamine/NMDA interactions , 1994, Trends in Neurosciences.

[48]  H. Sugiya,et al.  Understanding salivary fluid and protein secretion. , 2002, Oral diseases.

[49]  J. Wess,et al.  Dysregulated hippocampal acetylcholine neurotransmission and impaired cognition in M2, M4 and M2/M4 muscarinic receptor knockout mice , 2003, Molecular Psychiatry.

[50]  B. Masereel,et al.  Therapeutic potential of thromboxane inhibitors in asthma , 2002, Expert opinion on investigational drugs.

[51]  J. Wess.  Molecular biology of muscarinic acetylcholine receptors. , 1996, Critical reviews in neurobiology.

[52]  J. Wess,et al.  Roles of M2 and M3 muscarinic receptors in cholinergic nerve‐induced contractions in mouse ileum studied with receptor knockout mice , 2006, British journal of pharmacology.

[53]  Darrell R. Abernethy,et al.  International Union of Pharmacology: Approaches to the Nomenclature of Voltage-Gated Ion Channels , 2003, Pharmacological Reviews.

[54]  S. Hegde.  Muscarinic receptors in the bladder: from basic research to therapeutics , 2006, British journal of pharmacology.

[55]  J. Wess,et al.  M2 and M4 Receptor Knockout Mice: Muscarinic Receptor Function in Cardiac and Smooth Muscle In Vitro , 2000 .

[56]  A. Levey,et al.  The role of M1 muscarinic receptor agonism of N-desmethylclozapine in the unique clinical effects of clozapine , 2004, Psychopharmacology.

[57]  C. Langmead,et al.  Probing the Molecular Mechanism of Interaction between 4-n-Butyl-1-[4-(2-methylphenyl)-4-oxo-1-butyl]-piperidine (AC-42) and the Muscarinic M1 Receptor: Direct Pharmacological Evidence That AC-42 Is an Allosteric Agonist , 2006, Molecular Pharmacology.

[58]  P. Marin,et al.  GPCR interacting proteins (GIP). , 2004, Pharmacology & therapeutics.

[59]  M. Matsui,et al.  Increased Relaxant Action of Forskolin and Isoproterenol against Muscarinic Agonist-Induced Contractions in Smooth Muscle from M2 Receptor Knockout Mice , 2003, Journal of Pharmacology and Experimental Therapeutics.

[60]  M. Hasselmo.  The role of acetylcholine in learning and memory , 2006, Current Opinion in Neurobiology.

[61]  K. Mikoshiba,et al.  Up-Regulated PAR-2-Mediated Salivary Secretion in Mice Deficient in Muscarinic Acetylcholine Receptor Subtypes , 2007, Journal of Pharmacology and Experimental Therapeutics.

[62]  S. Kahn.  Clinical review 135: The importance of beta-cell failure in the development and progression of type 2 diabetes. , 2001, The Journal of clinical endocrinology and metabolism.

[63]  J. Sweatt,et al.  Molecular psychology: roles for the ERK MAP kinase cascade in memory. , 2002, Annual review of pharmacology and toxicology.

[64]  A. Parent,et al.  Facilitation of acetylcholine release and cognitive performance by an M(2)-muscarinic receptor antagonist in aged memory-impaired , 1995, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[65]  S. Yamada,et al.  Functional analysis of muscarinic acetylcholine receptors using knockout mice. , 2004, Life sciences.

[66]  J. Wess,et al.  Muscarinic stimulation of pancreatic insulin and glucagon release is abolished in m3 muscarinic acetylcholine receptor-deficient mice. , 2004, Diabetes.

[67]  A Carlsson,et al.  The current status of the dopamine hypothesis of schizophrenia. , 1988, Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology.

[68]  J. Wess,et al.  Role for M5 muscarinic acetylcholine receptors in cocaine addiction , 2003, Journal of neuroscience research.

[69]  R. Bartus,et al.  On Neurodegenerative Diseases, Models, and Treatment Strategies: Lessons Learned and Lessons Forgotten a Generation Following the Cholinergic Hypothesis , 2000, Experimental Neurology.

[70]  J. Wess,et al.  M1 Muscarinic Acetylcholine Receptors Activate Extracellular Signal-Regulated Kinase in CA1 Pyramidal Neurons in Mouse Hippocampal Slices , 2001, Molecular and Cellular Neuroscience.

[71]  M. Matsui,et al.  Cholinergically stimulated gastric acid secretion is mediated by M(3) and M(5) but not M(1) muscarinic acetylcholine receptors in mice. , 2005, American journal of physiology. Gastrointestinal and liver physiology.

[72]  A. Yamanaka,et al.  Mice lacking the M3 muscarinic acetylcholine receptor are hypophagic and lean , 2001, Nature.

[73]  J. Wess,et al.  Pronounced pharmacologic deficits in M2 muscarinic acetylcholine receptor knockout mice. , 1999, Proceedings of the National Academy of Sciences of the United States of America.

[74]  A. Christopoulos,et al.  Cellular Signaling Mechanisms for Muscarinic Acetylcholine Receptors , 2003 .

[75]  A. Fisher,et al.  M1 muscarinic agonists can modulate some of the hallmarks in Alzheimer’s disease , 2007, Journal of Molecular Neuroscience.

[76]  A. IJzerman,et al.  Allosteric modulation of G protein-coupled receptors. , 2001, Current opinion in drug discovery & development.

[77]  S. Itohara,et al.  Loss of M5 muscarinic acetylcholine receptors leads to cerebrovascular and neuronal abnormalities and cognitive deficits in mice , 2006, Neurobiology of Disease.

[78]  R. Eglen,et al.  Therapeutic opportunities from muscarinic receptor research. , 2001, Trends in pharmacological sciences.

[79]  C. S. Cbe.  Drug effects on salivary glands: dry mouth , 2003 .

[80]  Dinesh Gautam,et al.  Muscarinic acetylcholine receptor knockout mice show distinct synaptic plasticity impairments in the visual cortex , 2006, The Journal of physiology.

[81]  T. Sotnikova,et al.  Hyperactivity, elevated dopaminergic transmission, and response to amphetamine in M1 muscarinic acetylcholine receptor-deficient mice , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[82]  J. Wess,et al.  Beneficial metabolic effects of M3 muscarinic acetylcholine receptor deficiency. , 2006, Cell metabolism.

[83]  J. Ellis,et al.  Development of muscarinic analgesics derived from epibatidine: role of the M4 receptor subtype. , 1999, The Journal of pharmacology and experimental therapeutics.

[84]  G. Carey,et al.  SCH 57790, a selective muscarinic M(2) receptor antagonist, releases acetylcholine and produces cognitive enhancement in laboratory animals. , 2001, European journal of pharmacology.

[85]  U. Hacksell,et al.  Discovery of an ectopic activation site on the M(1) muscarinic receptor. , 2002, Molecular pharmacology.

[86]  M. Matsui,et al.  Impaired gastric secretion and lack of trophic responses to hypergastrinemia in M3 muscarinic receptor knockout mice. , 2003, Gastroenterology.

[87]  P. Hartvig,et al.  Cholinergic mechanisms in pain and analgesia. , 1989, Trends in pharmacological sciences.

[88]  Y. Konttinen,et al.  Use of muscarinic agonists in the treatment of Sjögren's syndrome. , 2001, Clinical immunology.

[89]  N. Nathanson,et al.  The M1 Receptor Is Required for Muscarinic Activation of Mitogen-activated Protein (MAP) Kinase in Murine Cerebral Cortical Neurons* , 2001, The Journal of Biological Chemistry.

[90]  J. Wess,et al.  Cholinergic dilation of cerebral blood vessels is abolished in M5 muscarinic acetylcholine receptor knockout mice , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[91]  J. Wess,et al.  Hyperactivity and Intact Hippocampus-Dependent Learning in Mice Lacking the M1 Muscarinic Acetylcholine Receptor , 2001, The Journal of Neuroscience.

[92]  J. Wess,et al.  Reduced Cocaine Self-Administration in Muscarinic M5 Acetylcholine Receptor-Deficient Mice , 2005, The Journal of Neuroscience.

[93]  R. Eglen.  Muscarinic receptor subtype pharmacology and physiology. , 2005, Progress in medicinal chemistry.

[94]  A. Beaudet,et al.  Synergistic control of keratinocyte adhesion through muscarinic and nicotinic acetylcholine receptor subtypes. , 2004, Experimental cell research.

[95]  J. Wess,et al.  Role of muscarinic receptor subtypes in the constriction of peripheral airways: studies on receptor-deficient mice. , 2003, Molecular pharmacology.

[96]  M. Kano,et al.  Postsynaptic M1 and M3 receptors are responsible for the muscarinic enhancement of retrograde endocannabinoid signalling in the hippocampus , 2003, The European journal of neuroscience.

[97]  N. Birdsall,et al.  International Union of Pharmacology. XVII. Classification of muscarinic acetylcholine receptors. , 1998, Pharmacological reviews.

[98]  J. Palacios,et al.  Localization of m5 muscarinic receptor mRNA in rat brain examined by in situ hybridization histochemistry , 1990, Neuroscience Letters.

[99]  J. Swanson,et al.  Attention deficit/hyperactivity disorder: characteristics, interventions and models. , 2000, Neurotoxicology and teratology.

[100]  F. Bymaster,et al.  Elucidating the role of muscarinic receptors in psychosis. , 2001, Life sciences.

[101]  Gary Kay,et al.  Muscarinic receptors: their distribution and function in body systems, and the implications for treating overactive bladder , 2006, British journal of pharmacology.

[102]  J. Yeomans,et al.  Increased drinking in mutant mice with truncated M5 muscarinic receptor genes , 2002, Pharmacology Biochemistry and Behavior.

[103]  P. Barnes.  Muscarinic receptor subtypes in airways. , 1993, Life sciences.

[104]  P. Reeh,et al.  Excitatory Nicotinic and Desensitizing Muscarinic (M2) Effects on C-Nociceptors in Isolated Rat Skin , 2001, The Journal of Neuroscience.

[105]  F. Bymaster,et al.  Butylthio[2.2.2] (NNC 11-1053/LY297802): an orally active muscarinic agonist analgesic. , 1997, The Journal of pharmacology and experimental therapeutics.

[106]  K. Nonogaki,et al.  New insights into sympathetic regulation of glucose and fat metabolism , 2000, Diabetologia.

[107]  J. Wess,et al.  Functional Activity of the M 2 and M 4 Receptor Subtypes in the Spinal Cord Studied with Muscarinic Acetylcholine Receptor Knockout Mice , 2005 .

[108]  J. Wess,et al.  Functional roles of muscarinic M2 and M3 receptors in mouse stomach motility: studies with muscarinic receptor knockout mice. , 2007, European journal of pharmacology.

[109]  E C Hulme,et al.  Scanning mutagenesis studies of the M1 muscarinic acetylcholine receptor. , 2003, Receptors & channels.

[110]  F. Bloom,et al.  Neuroscience of Addiction , 1998, Neuron.

[111]  M. Segal,et al.  Muscarinic receptors involved in hippocampal plasticity. , 1997, Life sciences.

[112]  B. Bloch,et al.  Phenotypical characterization of the rat striatal neurons expressing muscarinic receptor genes , 1992, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[113]  S. Lazareno,et al.  Thiochrome enhances acetylcholine affinity at muscarinic M4 receptors: receptor subtype selectivity via cooperativity rather than affinity. , 2004, Molecular pharmacology.

[114]  R. Quirion,et al.  Muscarinic receptor subtypes in human neurodegenerative disorders: focus on Alzheimer's disease. , 1989, Trends in pharmacological sciences.

[115]  A. Fryer,et al.  Muscarinic acetylcholine receptors and airway diseases. , 2003, Pharmacology & therapeutics.

[116]  C. Strader,et al.  Facilitation of acetylcholine release and improvement in cognition by a selective M2 muscarinic antagonist, SCH 72788. , 2001, Life sciences.

[117]  M. Caulfield.  Muscarinic receptors--characterization, coupling and function. , 1993, Pharmacology & therapeutics.

[118]  A. Levey,et al.  Immunological localization of m1-m5 muscarinic acetylcholine receptors in peripheral tissues and brain. , 1993, Life sciences.

[119]  H. Moutsopoulos,et al.  The management of Sjögren's syndrome , 2006, Nature Clinical Practice Rheumatology.

[120]  H. Kurzen,et al.  The Non-neuronal Cholinergic System of Human Skin , 2007, Hormone and metabolic research = Hormon- und Stoffwechselforschung = Hormones et metabolisme.

[121]  S. Lazareno,et al.  Allosterism at muscarinic receptors: ligands and mechanisms. , 2005, Mini reviews in medicinal chemistry.

[122]  J. Wess,et al.  M2 Muscarinic Acetylcholine Receptor Knock-Out Mice Show Deficits in Behavioral Flexibility, Working Memory, and Hippocampal Plasticity , 2004, The Journal of Neuroscience.

[123]  J. Wess,et al.  Functional Activity of the M2 and M4 Receptor Subtypes in the Spinal Cord Studied with Muscarinic Acetylcholine Receptor Knockout Mice , 2005, Journal of Pharmacology and Experimental Therapeutics.

[124]  N. Nathanson.  A multiplicity of muscarinic mechanisms: enough signaling pathways to take your breath away. , 2000, Proceedings of the National Academy of Sciences of the United States of America.

[125]  Masahiko Watanabe,et al.  Two distinct classes of muscarinic action on hippocampal inhibitory synapses: M2‐mediated direct suppression and M1/M3‐mediated indirect suppression through endocannabinoid signalling , 2004, The European journal of neuroscience.

[126]  J. Wess,et al.  A critical role for beta cell M3 muscarinic acetylcholine receptors in regulating insulin release and blood glucose homeostasis in vivo. , 2006, Cell metabolism.

[127]  J. Gomeza,et al.  M(2) and M(4) receptor knockout mice: muscarinic receptor function in cardiac and smooth muscle in vitro. , 2000, The Journal of pharmacology and experimental therapeutics.

[128]  Makoto M Taketo,et al.  Loss of anti-cataleptic effect of scopolamine in mice lacking muscarinic acetylcholine receptor subtype 4. , 2003, European journal of pharmacology.

[129]  S. B. Caine,et al.  Decreased prepulse inhibition and increased sensitivity to muscarinic, but not dopaminergic drugs in M5 muscarinic acetylcholine receptor knockout mice , 2007, Psychopharmacology.

[130]  J. Wess,et al.  Muscarinic Induction of Hippocampal Gamma Oscillations Requires Coupling of the M1 Receptor to Two Mixed Cation Currents , 2002, Neuron.

[131]  J. Wess,et al.  Deletion of the M5 muscarinic acetylcholine receptor attenuates morphine reinforcement and withdrawal but not morphine analgesia , 2002, Proceedings of the National Academy of Sciences of the United States of America.

[132]  B. Dean,et al.  Altered Hippocampal Muscarinic M4, but Not M1, Receptor Expression from Subjects with Schizophrenia , 2007, Biological Psychiatry.

[133]  Yunfeng Zhang,et al.  Decreased input-specific plasticity of the auditory cortex in mice lacking M1 muscarinic acetylcholine receptors. , 2006, Cerebral cortex.

[134]  Christian C Felder,et al.  Evaluation of muscarinic agonist-induced analgesia in muscarinic acetylcholine receptor knockout mice. , 2002, Molecular pharmacology.

[135]  P. Reeh,et al.  Muscarinic M2 receptors inhibit heat-induced CGRP release from isolated rat skin , 2001, Neuroreport.