23 Muscarinic Acetylcholine Receptor

Muscarinic acetylcholine receptors (muscarinic receptors) are prototypical G protein-coupled receptors (GPCRs) activated by the endogenous neurotransmitter acetylcholine and play key roles in regulating the activity of many vital functions of the central and peripheral nervous systems. Studies of muscarinic receptors as well as rhodopsin and b adrenergic receptors have revealed several characteristics of GPCRs, which are also true for other GPCRs. Here, we present an overview of the historical background and current studies of muscarinic receptors focusing on studies carried out in our laboratory. List of Abbreviations: AC, adenylyl cyclase; AKAP, cAMP-dependent protein kinase anchoring protein; GAP, GTPase-activating protein; GPCR, G protein-coupled receptor; GRK, G protein-coupled receptor kinase; i2, second intracellular loop; i3, third intracellular loop; IP3, inositol-1,4,5-trisphosphate; KO, knockout; NMR, nuclear magnetic resonance; PKA, cAMP-dependent protein kinase; PKC, protein kinase 3 Muscarinic acetylcholine receptor C; PLC, phospholipase C; RGS, regulators of G protein signaling; RH, regulator of G protein signaling homology; TM, transmembrane; TRPC6, transient receptor potential-canonical subtype; WT, wild-type

[1]  P. Carter.  Site-Directed Mutagenesis , 2020, Definitions.

[2]  Y. Hashimoto,et al.  Muscarinic M4 Receptor Recycling Requires a Motif in the Third Intracellular Loop , 2008, Journal of Pharmacology and Experimental Therapeutics.

[3]  Y. Kubo,et al.  Alternative splicing of RGS8 gene changes the binding property to the M1 muscarinic receptor to confer receptor type‐specific Gq regulation , 2006, Journal of neurochemistry.

[4]  J. Kim,et al.  Muscarinic acetylcholine receptors stimulate Ca2+ influx in PC12D cells predominantly via activation of Ca2+ store-operated channels. , 2006, Journal of biochemistry.

[5]  M. Shirakawa,et al.  The structure of the third intracellular loop of the muscarinic acetylcholine receptor M2 subtype , 2006, FEBS letters.

[6]  T. Kozasa,et al.  Snapshot of Activated G Proteins at the Membrane: The Gαq-GRK2-Gßγ Complex , 2005, Science.

[7]  L. Langeberg,et al.  Distinct enzyme combinations in AKAP signalling complexes permit functional diversity , 2005, Nature Cell Biology.

[8]  J. Kim,et al.  Activation of M1 Muscarinic Acetylcholine Receptors Stimulates the Formation of a Multiprotein Complex Centered on TRPC6 Channels* , 2005, Journal of Biological Chemistry.

[9]  J. Wess,et al.  Random Mutagenesis of the M3 Muscarinic Acetylcholine Receptor Expressed in Yeast , 2005, Journal of Biological Chemistry.

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

[11]  Jonathan A Javitch,et al.  The Ants Go Marching Two by Two: Oligomeric Structure of G-Protein-Coupled Receptors , 2004, Molecular Pharmacology.

[12]  D. Roberts,et al.  G protein activation by G protein coupled receptors: ternary complex formation or catalyzed reaction? , 2004, Biochemical pharmacology.

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

[14]  Graeme Milligan,et al.  G Protein-Coupled Receptor Dimerization: Function and Ligand Pharmacology , 2004, Molecular Pharmacology.

[15]  A. Levey,et al.  RGS2 Binds Directly and Selectively to the M1 Muscarinic Acetylcholine Receptor Third Intracellular Loop to Modulate Gq/11α Signaling* , 2004, Journal of Biological Chemistry.

[16]  S. Takeda,et al.  Stimulation of increases in intracellular calcium and prostaglandin E2 generation in Chinese hamster ovary cells expressing receptor-Galpha16 fusion proteins. , 2004, Journal of biochemistry.

[17]  P. H. Anborgh,et al.  G Protein-coupled Receptor Kinase 2 Regulator of G Protein Signaling Homology Domain Binds to Both Metabotropic Glutamate Receptor 1a and Gαq to Attenuate Signaling* , 2004, Journal of Biological Chemistry.

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

[19]  J. Buccafusco,et al.  The Cholinergic Hypothesis of Age and Alzheimer's Disease-Related Cognitive Deficits: Recent Challenges and Their Implications for Novel Drug Development , 2003, Journal of Pharmacology and Experimental Therapeutics.

[20]  J. Hepler.  RGS protein and G protein interactions: a little help from their friends. , 2003, Molecular pharmacology.

[21]  R. Lefkowitz,et al.  Keeping G Proteins at Bay: A Complex Between G Protein-Coupled Receptor Kinase 2 and Gßγ , 2003, Science.

[22]  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.

[23]  Christian C. Felder,et al.  Use of M1–M5 Muscarinic Receptor Knockout Mice as Novel Tools to Delineate the Physiological Roles of the Muscarinic Cholinergic System , 2003, Neurochemical Research.

[24]  A. Engel,et al.  Atomic-force microscopy: Rhodopsin dimers in native disc membranes , 2003, Nature.

[25]  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.

[26]  Shigeyuki Yokoyama,et al.  Conformation of ligands bound to the muscarinic acetylcholine receptor. , 2002, Molecular pharmacology.

[27]  K. Palczewski,et al.  Crystal Structure of Rhodopsin: A G‐Protein‐Coupled Receptor , 2002, Chembiochem : a European journal of chemical biology.

[28]  T. Fenton,et al.  Oligomerization of G-protein-coupled Receptors Shown by Selective Co-immunoprecipitation* , 2002, The Journal of Biological Chemistry.

[29]  J. Saldanha,et al.  Seven-transmembrane receptors: crystals clarify. , 2002, Trends in pharmacological sciences.

[30]  J. Wess,et al.  Conformational Changes That Occur during M3Muscarinic Acetylcholine Receptor Activation Probed by the Use of an in Situ Disulfide Cross-linking Strategy* , 2002, The Journal of Biological Chemistry.

[31]  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.

[32]  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.

[33]  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.

[34]  J W Saldanha,et al.  Transmembrane Domains 4 and 7 of the M1Muscarinic Acetylcholine Receptor Are Critical for Ligand Binding and the Receptor Activation Switch* , 2001, The Journal of Biological Chemistry.

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

[36]  P Ghanouni,et al.  Agonist-induced conformational changes in the G-protein-coupling domain of the β2 adrenergic receptor , 2001, Proceedings of the National Academy of Sciences of the United States of America.

[37]  D. Saffen,et al.  Muscarinic Acetylcholine Receptor Regulation of TRP6 Ca2+ Channel Isoforms , 2001, The Journal of Biological Chemistry.

[38]  S. Takeda,et al.  Receptor-Gα fusion proteins as a tool for ligand screening , 2001 .

[39]  F Guarnieri,et al.  Agonist-induced Conformational Changes at the Cytoplasmic Side of Transmembrane Segment 6 in the β2 Adrenergic Receptor Mapped by Site-selective Fluorescent Labeling* , 2001, The Journal of Biological Chemistry.

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

[41]  K. Broadley,et al.  Muscarinic Receptor Agonists and Antagonists , 2001, Molecules : A Journal of Synthetic Chemistry and Natural Product Chemistry.

[42]  A. Krogh,et al.  Predicting transmembrane protein topology with a hidden Markov model: application to complete genomes. , 2001, Journal of molecular biology.

[43]  L. Laurier,et al.  Pharmacological and molecular characterization of muscarinic receptor subtypes in human esophageal smooth muscle. , 2000, The Journal of pharmacology and experimental therapeutics.

[44]  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.

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

[46]  E. Hulme,et al.  A Network of Conserved Intramolecular Contacts Defines the Off-state of the Transmembrane Switch Mechanism in a Seven-transmembrane Receptor* , 2000, The Journal of Biological Chemistry.

[47]  J L Benovic,et al.  Regulation of G protein-coupled receptor kinases. , 2000, Trends in cardiovascular medicine.

[48]  L. Parnetti,et al.  Radioligand binding assay of M1–M5 muscarinic cholinergic receptor subtypes in human peripheral blood lymphocytes , 1999, Journal of Neuroimmunology.

[49]  B. Kobilka,et al.  GPCR–Gα fusion proteins: molecular analysis of receptor–G-protein coupling , 1999 .

[50]  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.

[51]  R. Buchli,et al.  Human skin fibroblasts express m2, m4, and m5 subtypes of muscarinic acetylcholine receptors , 1999, Journal of cellular biochemistry.

[52]  J. Wess,et al.  Identification and Molecular Characterization of m3 Muscarinic Receptor Dimers* , 1999, The Journal of Biological Chemistry.

[53]  A Olivier,et al.  Functional Acetylcholine Muscarinic Receptor Subtypes in Human Brain Microcirculation: Identification and Cellular Localization , 1999, Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism.

[54]  O. Lichtarge,et al.  Similar structures and shared switch mechanisms of the beta2-adrenoceptor and the parathyroid hormone receptor. Zn(II) bridges between helices III and VI block activation. , 1999, The Journal of biological chemistry.

[55]  J. Wess,et al.  Conserved Extracellular Cysteine Pair in the M3 Muscarinic Acetylcholine Receptor Is Essential for Proper Receptor Cell Surface Localization but Not for G Protein Coupling , 1999, Journal of neurochemistry.

[56]  S. Lazareno,et al.  Subtype-selective positive cooperative interactions between brucine analogs and acetylcholine at muscarinic receptors: functional studies. , 1999, Molecular pharmacology.

[57]  E C Hulme,et al.  The Functional Topography of Transmembrane Domain 3 of the M1 Muscarinic Acetylcholine Receptor, Revealed by Scanning Mutagenesis* , 1999, The Journal of Biological Chemistry.

[58]  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.

[59]  B S Brown,et al.  KCNQ2 and KCNQ3 potassium channel subunits: molecular correlates of the M-channel. , 1998, Science.

[60]  J. Behr,et al.  Effect of N-glycosylation on production of the rat m3 muscarinic acetylcholine receptor in baculovirus-infected insect cells. , 1998, Biochemical Society transactions.

[61]  K. Kameyama,et al.  Desensitization of human muscarinic acetylcholine receptor m2 subtypes is caused by their sequestration/internalization. , 1998, Journal of biochemistry.

[62]  K. Kameyama,et al.  Sequestration of human muscarinic acetylcholine receptor hm1-hm5 subtypes: effect of G protein-coupled receptor kinases GRK2, GRK4, GRK5 and GRK6. , 1998, The Journal of pharmacology and experimental therapeutics.

[63]  K. Kameyama,et al.  Internalization and Down-regulation of Human Muscarinic Acetylcholine Receptor m2 Subtypes , 1998, The Journal of Biological Chemistry.

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

[65]  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.

[66]  E. Woldemussie,et al.  Muscarinic receptor subtypes in human iris-ciliary body measured by immunoprecipitation. , 1997, Investigative ophthalmology & visual science.

[67]  S. Sprang,et al.  Structure of RGS4 Bound to AlF4 −-Activated Giα1: Stabilization of the Transition State for GTP Hydrolysis , 1997, Cell.

[68]  M. Hayashi,et al.  Palmitoylation of muscarinic acetylcholine receptor m2 subtypes: reduction in their ability to activate G proteins by mutation of a putative palmitoylation site, cysteine 457, in the carboxyl-terminal tail. , 1997, Archives of biochemistry and biophysics.

[69]  J. Alderfer,et al.  The first and second cytoplasmic loops of the G-protein receptor, rhodopsin, independently form beta-turns. , 1997, Biochemistry.

[70]  J. Wess,et al.  Structural basis of receptor/G protein coupling selectivity studied with muscarinic receptors as model systems. , 1997, Life sciences.

[71]  J. Wess,et al.  Molecular basis of receptor/G protein coupling selectivity studied by coexpression of wild type and mutant m2 muscarinic receptors with mutant G alpha(q) subunits. , 1997, Biochemistry.

[72]  J. Phillips,et al.  Variation in mRNA expression of alpha-adrenergic, neurokinin and muscarinic receptors amongst four arteries of the rat. , 1997, Journal of the autonomic nervous system.

[73]  H. Khorana,et al.  Requirement of Rigid-Body Motion of Transmembrane Helices for Light Activation of Rhodopsin , 1996, Science.

[74]  O. Lichtarge,et al.  Rhodopsin activation blocked by metal-ion-binding sites linking transmembrane helices C and F , 1996, Nature.

[75]  H. Khorana,et al.  Structural features and light-dependent changes in the cytoplasmic interhelical E-F loop region of rhodopsin: a site-directed spin-labeling study. , 1996, Biochemistry.

[76]  G. Makhlouf,et al.  Somatostatin Receptor-mediated Signaling in Smooth Muscle , 1996, The Journal of Biological Chemistry.

[77]  C. Fraser,et al.  Alanine scanning mutagenesis of conserved arginine/lysine-arginine/lysine-X-X-arginine/lysine G protein-activating motifs on m1 muscarinic acetylcholine receptors. , 1996, Molecular pharmacology.

[78]  M. Olianas,et al.  Rat striatal muscarinic receptors coupled to the inhibition of adenylyl cyclase activity: potent block by the selective m4 ligand muscarinic toxin 3 (MT3) , 1996, British journal of pharmacology.

[79]  F. Amenta,et al.  Muscarinic cholinergic receptor subtypes in human peripheral blood lymphocytes , 1996, Neuroscience Letters.

[80]  M. Brann,et al.  Structure of a G-protein-coupling Domain of a Muscarinic Receptor Predicted by Random Saturation Mutagenesis (*) , 1996, The Journal of Biological Chemistry.

[81]  J. Wess,et al.  Identification of a receptor/G-protein contact site critical for signaling specificity and G-protein activation. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[82]  J. Alderfer,et al.  Structure of the third cytoplasmic loop of bovine rhodopsin. , 1995, Biochemistry.

[83]  J. Proska,et al.  Competition between positive and negative allosteric effectors on muscarinic receptors. , 1995, Molecular pharmacology.

[84]  N Blin,et al.  Mapping of Single Amino Acid Residues Required for Selective Activation of G by the m3 Muscarinic Acetylcholine Receptor (*) , 1995, The Journal of Biological Chemistry.

[85]  H. Khorana,et al.  Mapping light-dependent structural changes in the cytoplasmic loop connecting helices C and D in rhodopsin: a site-directed spin labeling study. , 1995, Biochemistry.

[86]  H. Lester,et al.  Evidence that neuronal G-protein-gated inwardly rectifying K+ channels are activated by G beta gamma subunits and function as heteromultimers. , 1995, Proceedings of the National Academy of Sciences of the United States of America.

[87]  D. Traver,et al.  Identification of m3, m4 and m5 subtypes of muscarinic receptor mRNA in human blood mononuclear cells , 1995, Journal of Neuroimmunology.

[88]  D. Clapham.  Replenishing the stores , 1995, Nature.

[89]  J. Proska,et al.  Allosteric modulation of muscarinic acetylcholine receptors. , 1995, Trends in pharmacological sciences.

[90]  W. Sadee,et al.  Activating and Inactivating Mutations in N- and C-terminal i3 Loop Junctions of Muscarinic Acetylcholine Hm1 Receptors (*) , 1995, The Journal of Biological Chemistry.

[91]  K. Kameyama,et al.  Characterization of G Family G Proteins G (G), G (G), and G Expressed in the Baculovirus-Insect Cell System (*) , 1995, The Journal of Biological Chemistry.

[92]  J. Wess,et al.  Muscarinic acetylcholine receptors: structural basis of ligand binding and G protein coupling. , 1995, Life sciences.

[93]  J. Benovic,et al.  Agonist-dependent phosphorylation of human muscarinic receptors in Spodoptera frugiperda insect cell membranes by G protein-coupled receptor kinases. , 1995, Molecular pharmacology.

[94]  R. Taussig,et al.  Mammalian Membrane-bound Adenylyl Cyclases (*) , 1995, The Journal of Biological Chemistry.

[95]  K. Kameyama,et al.  Sequestration of muscarinic acetylcholine receptor m2 subtypes. Facilitation by G protein-coupled receptor kinase (GRK2) and attenuation by a dominant-negative mutant of GRK2. , 1994, The Journal of biological chemistry.

[96]  K. Kameyama,et al.  Activation of a GTP-binding protein and a GTP-binding-protein-coupled receptor kinase (beta-adrenergic-receptor kinase-1) by a muscarinic receptor m2 mutant lacking phosphorylation sites. , 1994, European journal of biochemistry.

[97]  A. Strosberg,et al.  Cellular signaling by an agonist-activated receptor/Gs alpha fusion protein. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[98]  J. Buccafusco,et al.  m1–m5 Muscarinic Receptor Distribution in Rat CNS by RT‐PCR and HPLC , 1994, Journal of neurochemistry.

[99]  J. Wess,et al.  Insertion mutagenesis as a tool to predict the secondary structure of a muscarinic receptor domain determining specificity of G-protein coupling. , 1994, Proceedings of the National Academy of Sciences of the United States of America.

[100]  K. Kameyama,et al.  G Protein‐Coupled Receptor Kinases , 1994 .

[101]  M. Eck,et al.  Role of acidic amino acids in the allosteric modulation by gallamine of antagonist binding at the m2 muscarinic acetylcholine receptor. , 1994, Molecular pharmacology.

[102]  T. Wieland,et al.  Transfected muscarinic acetylcholine receptors selectively couple to Gi-type G proteins and Gq/11. , 1994, Molecular pharmacology.

[103]  K. Kameyama,et al.  Synergistic activation of a G protein-coupled receptor kinase by G protein beta gamma subunits and mastoparan or related peptides. , 1994, The Journal of biological chemistry.

[104]  R. Lefkowitz,et al.  Binding of G protein beta gamma-subunits to pleckstrin homology domains. , 1994, The Journal of biological chemistry.

[105]  J. Baldwin,et al.  Structure and function of receptors coupled to G proteins. , 1994, Current opinion in cell biology.

[106]  E. El-Fakahany,et al.  An arginine residue conserved in most G protein-coupled receptors is essential for the function of the m1 muscarinic receptor. , 1994, Molecular pharmacology.

[107]  K. Kameyama,et al.  Location of agonist-dependent-phosphorylation sites in the third intracellular loop of muscarinic acetylcholine receptors (m2 subtype). , 1994, European journal of biochemistry.

[108]  J. Benovic,et al.  Expression, purification, and characterization of the G protein-coupled receptor kinase GRK5. , 1994, The Journal of biological chemistry.

[109]  J. Wess,et al.  Identification of an intracellular tyrosine residue critical for muscarinic receptor-mediated stimulation of phosphatidylinositol hydrolysis. , 1994, The Journal of biological chemistry.

[110]  W. Sadee,et al.  Hydrophobic amino acid in the i2 loop plays a key role in receptor-G protein coupling. , 1993, The Journal of biological chemistry.

[111]  E. Peralta,et al.  Charged amino acids required for signal transduction by the m3 muscarinic acetylcholine receptor. , 1993, The EMBO journal.

[112]  M. Brann,et al.  Use of chimeric muscarinic receptors to investigate epitopes involved in allosteric interactions. , 1993, Molecular pharmacology.

[113]  J. Benovic,et al.  Phosphorylation and desensitization of human m2 muscarinic cholinergic receptors by two isoforms of the beta-adrenergic receptor kinase. , 1993, The Journal of biological chemistry.

[114]  K. Kameyama,et al.  Activation by G protein beta gamma subunits of beta-adrenergic and muscarinic receptor kinase. , 1993, The Journal of biological chemistry.

[115]  J. Baldwin.  The probable arrangement of the helices in G protein‐coupled receptors. , 1993, The EMBO journal.

[116]  J. Wess,et al.  Coexpression studies with mutant muscarinic/adrenergic receptors provide evidence for intermolecular "cross-talk" between G-protein-linked receptors. , 1993, Proceedings of the National Academy of Sciences of the United States of America.

[117]  S. Rhee,et al.  Activation of phospholipase C isozymes by G protein beta gamma subunits. , 1993, The Journal of biological chemistry.

[118]  R. Yasuda,et al.  Development of antisera selective for m4 and m5 muscarinic cholinergic receptors: distribution of m4 and m5 receptors in rat brain. , 1993, Molecular pharmacology.

[119]  M. Camps,et al.  Activation of phosphatidylinositol lipid‐specific phospholipase C‐β3 by G‐protein βγ subunits , 1993 .

[120]  J. Wess,et al.  Functional role of proline and tryptophan residues highly conserved among G protein‐coupled receptors studied by mutational analysis of the m3 muscarinic receptor. , 1993, The EMBO journal.

[121]  M. Simon,et al.  Subunits βγ of heterotrimeric G protein activate β2 isoform of phospholipase C , 1992, Nature.

[122]  M. Camps,et al.  Isozyme-selective stimulation of phospholipase C-β2 by G protein βγ-subunits , 1992, Nature.

[123]  R. Richardson,et al.  Agonist-induced phosphorylation and desensitization of human m2 muscarinic cholinergic receptors in Sf9 insect cells. , 1992, The Journal of biological chemistry.

[124]  T. Haga,et al.  Effects of magnesium ion on the interaction of atrial muscarinic acetylcholine receptors and GTP-binding regulatory proteins. , 1992, Biochemistry.

[125]  J. Wess,et al.  Role of conserved threonine and tyrosine residues in acetylcholine binding and muscarinic receptor activation. A study with m3 muscarinic receptor point mutants. , 1992, The Journal of biological chemistry.

[126]  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.

[127]  J. B. Higgins,et al.  Role of beta gamma subunits of G proteins in targeting the beta-adrenergic receptor kinase to membrane-bound receptors. , 1992, Science.

[128]  E. Ross,et al.  Phospholipase C-β1 is a GTPase-activating protein for Gq/11, its physiologic regulator , 1992, Cell.

[129]  C. Fraser,et al.  Site-directed mutagenesis of the rat m1 muscarinic acetylcholine receptor. Role of conserved cysteines in receptor function. , 1992, The Journal of biological chemistry.

[130]  M. Olianas,et al.  Properties of Muscarinic‐Stimulated Adenylate Cyclase Activity in Rat Olfactory Bulb , 1992, Journal of neurochemistry.

[131]  E. Ross,et al.  Reconstitution of agonist-stimulated phosphatidylinositol 4,5-bisphosphate hydrolysis using purified m1 muscarinic receptor, Gq/11, and phospholipase C-beta 1. , 1992, The Journal of biological chemistry.

[132]  T. Haga,et al.  Activation by G protein beta gamma subunits of agonist- or light-dependent phosphorylation of muscarinic acetylcholine receptors and rhodopsin. , 1992, The Journal of biological chemistry.

[133]  J. Wess,et al.  Site‐directed mutagenesis of the m3 muscarinic receptor: identification of a series of threonine and tyrosine residues involved in agonist but not antagonist binding. , 1991, The EMBO journal.

[134]  J. Kukkonen,et al.  Muscarinic receptor-linked elevation of cAMP in SH-SY5Y neuroblastoma cells is mediated by Ca2+ and protein kinase C. , 1991, Biochimica et biophysica acta.

[135]  D. Price,et al.  Identification and localization of muscarinic acetylcholine receptor proteins in brain with subtype-specific antibodies , 1991, The Journal of neuroscience : the official journal of the Society for Neuroscience.

[136]  A. Levey,et al.  Immunological detection of muscarinic receptor subtype proteins (m1-m5) in rabbit peripheral tissues. , 1991, Molecular pharmacology.

[137]  M. Caron,et al.  Role of acidic amino acids in peptide substrates of the beta-adrenergic receptor kinase and rhodopsin kinase. , 1991, Biochemistry.

[138]  E. Ginns,et al.  Production of antisera selective for m1 muscarinic receptors using fusion proteins: distribution of m1 receptors in rat brain. , 1991, Molecular pharmacology.

[139]  P C Sternweis,et al.  Regulation of polyphosphoinositide-specific phospholipase C activity by purified Gq. , 1991, Science.

[140]  K. Kameyama,et al.  Reconstitutively active G protein-coupled receptors purified from baculovirus-infected insect cells. , 1991, The Journal of biological chemistry.

[141]  T. Haga,et al.  Interaction of deglycosylated muscarinic receptors with ligands and G proteins. , 1990, European journal of pharmacology.

[142]  J. Wess,et al.  Delineation of muscarinic receptor domains conferring selectivity of coupling to guanine nucleotide-binding proteins and second messengers. , 1990, Molecular pharmacology.

[143]  A. Levey,et al.  Expression of muscarinic acetylcholine and dopamine receptor mRNAs in rat basal ganglia. , 1990, Proceedings of the National Academy of Sciences of the United States of America.

[144]  E. Hulme,et al.  Muscarinic acetylcholine receptors. Peptide sequencing identifies residues involved in antagonist binding and disulfide bond formation. , 1990, The Journal of biological chemistry.

[145]  T. Haga,et al.  Dual regulation by G proteins of agonist‐dependent phosphorylation of muscarinic acetylcholine receptors , 1990, FEBS letters.

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

[147]  T. Haga,et al.  Location in Muscarinic Acetylcholine Receptors of Sites for [3H]Propylbenzilcholine Mustard Binding and for Phosphorylation with Protein Kinase C , 1990, Journal of neurochemistry.

[148]  T. Haga,et al.  Phosphorylation by Protein Kinase C of the Muscarinic Acetylcholine Receptor , 1990, Journal of neurochemistry.

[149]  E. Ross,et al.  Chimeric muscarinic cholinergic: beta-adrenergic receptors that activate Gs in response to muscarinic agonists. , 1990, The Journal of biological chemistry.

[150]  T. Haga,et al.  Interaction of atrial muscarinic receptors with three kinds of GTP-binding proteins. , 1990, Journal of molecular and cellular cardiology.

[151]  Bonner Ti.  New subtypes of muscarinic acetylcholine receptors. , 1989 .

[152]  J. Venter,et al.  Site-directed mutagenesis of m1 muscarinic acetylcholine receptors: conserved aspartic acids play important roles in receptor function. , 1989, Molecular pharmacology.

[153]  J. Wess,et al.  Identification of a small intracellular region of the muscarinic m3 receptor as a determinant of selective coupling to PI turnover , 1989, FEBS letters.

[154]  T. Haga,et al.  AGONIST-DEPENDENT PHOSPHORYLATION OF CEREBRAL AND ATRIAL MUSCARINIC RECEPTORS: BLOCKADE OF THE PHOSPHORYLATION BY GTP-BINDING REGULATORY PROTEINS AND ITS REVERSAL BY GUANINE NUCLEOTIDES , 1989 .

[155]  N. Birdsall,et al.  Propylbenzilylcholine mustard labels an acidic residue in transmembrane helix 3 of the muscarinic receptor. , 1989, The Journal of biological chemistry.

[156]  T. Bonner,et al.  Cloning and expression of the human and rat m5 muscarinic acetylcholine receptor genes , 1988, Neuron.

[157]  A. Ashkenazi,et al.  Structural basis of muscarinic acetylcholine receptor subtype diversity. , 1988, Trends in pharmacological sciences.

[158]  T. Haga,et al.  Molecular properties of muscarinic receptors. , 1988, Trends in pharmacological sciences.

[159]  T. Bonner,et al.  Identification of a family of muscarinic acetylcholine receptor genes. , 1987, Science.

[160]  D. Clapham,et al.  The βγ subunits of GTP-binding proteins activate the muscarinic K+ channel in heart , 1987, Nature.

[161]  K. Sugimoto,et al.  Primary structure of porcine cardiac muscarinic acetylcholine receptor deduced from the cDNA sequence , 1986, FEBS letters.

[162]  M. Mishina,et al.  Cloning, sequencing and expression of complementary DNA encoding the muscarinic acetylcholine receptor , 1986, Nature.

[163]  T. Haga,et al.  Reconstitution of the muscarinic acetylcholine receptor. Guanine nucleotide-sensitive high affinity binding of agonists to purified muscarinic receptors reconstituted with GTP-binding proteins (Gi and Go). , 1986, The Journal of biological chemistry.

[164]  Brian K. Kobilka,et al.  Cloning of the gene and cDNA for mammalian β-adrenergic receptor and homology with rhodopsin , 1986, Nature.

[165]  T. Katada,et al.  Functional reconstitution of purified muscarinic receptors and inhibitory guanine nucleotide regulatory protein , 1985, Nature.

[166]  T. Haga,et al.  Purification of the muscarinic acetylcholine receptor from porcine brain. , 1985, The Journal of biological chemistry.

[167]  P. Sternweis,et al.  Reconstitution of resolved muscarinic cholinergic receptors with purified GTP-binding proteins. , 1985, The Journal of biological chemistry.

[168]  T. Haga,et al.  Affinity chromatography of the muscarinic acetylcholine receptor. , 1983, The Journal of biological chemistry.

[169]  J. Nathans,et al.  Isolation, sequence analysis, and intron-exon arrangement of the gene encoding bovine rhodopsin , 1983, Cell.

[170]  D L Price,et al.  Alzheimer's disease: a disorder of cortical cholinergic innervation. , 1983, Science.

[171]  R. Bartus,et al.  The cholinergic hypothesis of geriatric memory dysfunction. , 1982, Science.

[172]  B. Ilien,et al.  Solubilization of brain muscarinic, dopaminergic and serotonergic receptors: a critical analysis. , 1982, Biochemical pharmacology.

[173]  D. A. Brown,et al.  Muscarinic suppression of a novel voltage-sensitive K+ current in a vertebrate neurone , 1980, Nature.

[174]  N. Birdsall,et al.  Pirenzepine distinguishes between different subclasses of muscarinic receptors , 1980, Nature.

[175]  P. Pauling,et al.  Structure of Acetylcholine and Other Substrates of Cholinergic Systems , 1966, Nature.

[176]  H. Nakata,et al.  Purinergic-receptor oligomerization: Implications for neural functions in the central nervous system , 2009, Neurotoxicity Research.

[177]  I. Kramer,et al.  Effector enzymes coupled to GTP-binding proteins: Adenylyl cyclase and phospholipase C , 2009 .

[178]  C. Venkatachalam,et al.  LigandFit: a novel method for the shape-directed rapid docking of ligands to protein active sites. , 2003, Journal of molecular graphics & modelling.

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

[180]  J. Wess,et al.  M1-M5 muscarinic receptor knockout mice as novel tools to study the physiological roles of the muscarinic cholinergic system. , 2003, Receptors & channels.

[181]  W. Delano.  The PyMOL Molecular Graphics System , 2002 .

[182]  G. Milligan.  Construction and analysis of function of G protein-coupled receptor-G protein fusion proteins. , 2002, Methods in enzymology.

[183]  K. Kameyama,et al.  Regulation of G protein-coupled receptor kinase 2. , 2002, Methods in enzymology.

[184]  E M Ross,et al.  GTPase-activating proteins for heterotrimeric G proteins: regulators of G protein signaling (RGS) and RGS-like proteins. , 2000, Annual review of biochemistry.

[185]  S. Lazareno,et al.  Probing of the location of the allosteric site on m1 muscarinic receptors by site-directed mutagenesis. , 1995, Molecular pharmacology.

[186]  K. Kameyama,et al.  Phosphorylation of muscarinic receptors: regulation by G proteins. , 1993, Life sciences.

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

[188]  J. Baumgold,et al.  Agents that stimulate phosphoinositide turnover also elevate cAMP in SK-N-SH human neuroblastoma cells. , 1992, Life sciences.

[189]  A. Casy.  Stereochemical aspects of parasympathomimetics and their antagonists: recent developments. , 1975, Progress in medicinal chemistry.

[190]  M. Hassan,et al.  Conformation of some acetylcholine analogs as solutes in deuterium oxide and other solvents. , 1971, Journal of pharmaceutical sciences.

[191]  P. Portoghese.  Relationships between stereostructure and pharmacological activities. , 1970, Annual review of pharmacology.