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Molecular Aspects of Muscarinic Receptors

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Abstract

The effects of acetylcholine were classified by Dale (1914) into two groups: (a) the effects which were mimicked by administration of the alkaloid muscarine and selectively antagonized by atropine were termed muscarine-like or muscarinic effects; (b) the effects which were mimicked by administration of nicotine and not antagonized by atropine but blocked by other agents (for example, d-tubocurarine) were termed nicotine-like or nicotinic effects. Muscarinic effects resemble the responses to stimulation of parasympathetic nerves except those at the sweat glands and arterioles, which receive postganglionic sympathetic fibres. Muscarinic effects include contraction of the sphincter muscle of the iris (miosis) and of the ciliary muscle of the eye (for near vision), decrease in the heart rate, decrease in the contractility and shortening of the action potential in the atria, decrease in the conduction velocity of the A-V node, dilatation of the arterioles accompanied by lowering of the blood pressure, contraction of the tracheal and the bronchial muscle, increase in the motility and the tone of the stomach and the intestine, contraction of the gallbladder and the ducts, contraction of the detrussor and relaxation of the trigone and the sphincter in the urinary bladder, erection of the male sex organs, and stimulation of the secretion in the exocrine glands (nasopharyngeal glands, bronchial glands, salivary glands, stomach and intestine glands, pancreas, sweat glands and lacrimal glands).

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Notes

  • Akiba, I., Kubo, T., Maeda, A., Bujo, H., Nakai, J., Mishina, M. and Numa, S. (1988) Primary structure of porcine muscarinic acetylcholine receptor III and antagonist binding studies. FEBS Lett., 235, 257–261

    Google Scholar 

  • Allen, J. P., Feher, G., Yeates, T. O., Komiya, H. and Rees, D. C. (1987). Structure of the reaction center from Rhodobacter sphaeroides R-26: the protein subunits. Proc. Natl Acad. Sci. USA, 84, 6162–6166

    Google Scholar 

  • André, C., De Backer, J. P., Guillet, J. C., Vanderheyden, P., Vauquelin, G. and Strosberg, A. D. (1983). Purification of muscarinic acetylcholine receptors by affinity chromatography. EMBO Jl, 2, 499–504

    Google Scholar 

  • Applebury, M. L. and Hargrave, P. A. (1986). Molecular biology of the visual pigments. Vision Res., 26, 1881–1895

    Google Scholar 

  • Ashkenazi, A., Peralta, E. G., Winslow, J. W., Ramachandran, J. and Capon, D. J. (1988). Functionally distinct G proteins selectively couple different receptors to PI hydrolysis in the same cell. Cell, 56, 487–493

    Google Scholar 

  • Ashkenazi, A., Winslow, J. W., Peralta, E. G., Peterson, G. L., Schimerlik, M. I., Capon, D. J. and Ramachandran, J. (1987). An M2 muscarinic receptor subtype coupled to both adenylyl cyclase and phosphoinositide turnover. Science, N.Y., 238, 672–675

    Google Scholar 

  • Barnard, E. A. (1988). Separating receptor subtypes from their shadows. Nature, 335, 301–302

    Google Scholar 

  • Baron, B., Gavish, M. and Sokolovsky, M. (1985). Heterogeneity of solubilized muscarinic cholinergic receptors: binding and hydrodynamic properties. Arch. Biochem. Biophys., 240, 281–296

    Google Scholar 

  • Baumgold, J., Merril, C. and Gershon, E. S. (1987). Loss of pirenzepine regional selectivity following solubilization and partial purification of the putative M1and M2 muscarinic receptors subtypes. Molec. Brain Res., 2, 7–14

    Google Scholar 

  • Behling, R. W., Yamane, T., Navon, G. and Jelinski, L. W. (1988). Conformation of acetylcholine bound to the nichotinic acetylcholine receptor. Proc. Natl Acad. Sci. USA, 85, 6721–6725

    Google Scholar 

  • Beld, A. J. and Aliëns, E. J. (1974). Stereospecific binding as a tool in attempts to localize and isolate muscarinic receptors. Part II. Binding of (+)-benzetimide, (-)-benzetimide and atropine to a fraction from bovine tracheal smooth muscle and to bovine caudate nucleus. Eur. J. Pharmacol., 25, 203–209

    Google Scholar 

  • Benovic, J. L., Regan, J. W., Matsui, H., Mayor, F., Jr., Cotecchia, S., Leeb-Lundberg, L. M. F., Caron, M. G. and Lefkowitz, R. J. (1987). Agonist-dependent phophorylation of the α-adrenergic receptor by the β-adrenergic receptor kinase. J. Biol. Chem., 262, 17251–17253

    Google Scholar 

  • Benovic, J. L., Strader, R. H., Caron, M. G. and Lefkowitz, R. J. (1986). β-adrenergic receptor kinase: identification of a novel kinase that phosphorylates the agonist-occupied form of the receptor. Proc. Natl Acad. Sci. USA, 83, 2797–2801

    Google Scholar 

  • Berrie, C. P., Birdsall, N. J. M., Burgen, A. S. V. and Hulme, E. C. (1979). Guanine nucleotides modulate muscarinic receptor binding in the heart. Biochem. Biophys. Res. Commun., 87, 1000–1005

    Google Scholar 

  • Berrie, C. P., Birdsall, N. J. M., Dadi, H. K., Hulme, E. C., Morris, R. J., Stockton, J. M. and Wheatley, M. (1985). Purification of the muscarinic acetylcholine receptor from rat forebrain. Trans. Biochem. Soc, 13, 1101–1103

    Google Scholar 

  • Berrie, C. P., Birdsall, N. J. M., Hulme, E. C., Keen, M. and Stockton J. M. (1984). Solubilization and characterization of guanine nucleotide-sensitive muscarinic agonist binding sites from rat myocardium. Br. J. Pharmacol., 82, 853–861

    Google Scholar 

  • Berrie, C. P., Birdsall, N. J. M., Hulme, E. C., Keen, M., Stockton, J. M., and Wheatley, M. (1986). Muscarinic receptor subclasses: the binding properties of the soluble receptor binding sites. Trends Pharmacol. Sci. Suppl.: Subtypes of Muscarinic Receptors II, 8–13

    Google Scholar 

  • Berstein, G., Haga, K., Haga, T. and Ichiyama, A. (1988). Agonist and antagonist binding of muscarinic acetylcholine receptors purified from porcine brain: interconversion of high- and low-affinity sites by sulfhydryl reagents. J. Neurochem., 50, 1687–1694

    Google Scholar 

  • Berstein, G., Haga, T. and Ichiyama, A. (1989). Effect of the lipid environment on the differential affinity of purified cerebral and atrial muscarinic acetylcholine receptors for pirenzepine. Molec. Pharmacol., in press

    Google Scholar 

  • Birdsall, N. J. M. (1989). Receptor structure: the accelerating impact of molecular biology. Trends Pharmacol. Sci., 10, 50–52

    Google Scholar 

  • Birdsall, N. J. M., Burgen, A. S. V. and Hulme, E. C. (1978). The binding of agonists to brain muscarinic receptors. Molec. Pharmacol., 14, 723–736

    Google Scholar 

  • Birdsall, N. J. M., Burgen, A. S. V. and Hulme, E. C. (1979). A study of the muscarinic receptor by gel electrophoresis. Br. J. Pharmacol., 66, 337–342

    Google Scholar 

  • Birdsall, N. J. M., Hulme, E. C. and Keen, M. (1986). The binding of pirenzepine to digitonin-solubilized muscarinic acetylcholine receptors from the rat myocardium. Br. J. Pharmacol., 87, 307–316

    Google Scholar 

  • Birdsall, N. J. M., Hulme, E. C. and Stockton, J. M. (1984). Muscarinic receptor heterogeneity. Trends Pharmacol. Sci. Suppl.: Subtypes of Muscarinic Receptors I, 4–8

    Google Scholar 

  • Bonner, T. I. (1989). The molecular basis of muscarinic receptor diversity. Trends Neurosci., 12, 148–151

    Google Scholar 

  • Bonner, T. I., Buckley, N. J., Young, A. C. and Brann, M. R. (1987). Identification of a family of muscarinic acetylcholine receptor genes. Science, N. Y., 237, 527–532

    Google Scholar 

  • Bonner, T. I., Young, A. C., Brann, M. R. and Buckley, N. J. (1988). Cloning and expression of the human and rat m5 muscarinic acetylcholine receptor genes. Neuron, 1, 403–410

    Google Scholar 

  • Bouvier, M., Hausdorff, W. P., De Blasi, A., O’Dowd, B. F., Kobilka, B. K., Caron, M. G. and Lefkowitz, R. J. (1988). Removal of phosphorylation sites from the β2-adrenergic receptor delays onset of agonist-promoted desensitization. Nature, 333, 370–373

    Google Scholar 

  • Buckley, N. J., Bonner, T. I. and Brann, M. R. (1988). Localization of a family of muscarinic receptor mRNAs in rat brain. J. Neurosci., 8, 4646–4652

    Google Scholar 

  • Bujo, H., Nakai, J., Kubo, T., Fukuda, K., Akiba, I., Maeda, A., Mishina, M. and Numa, S. (1988). Different sensitivities to agonist of muscarinic acetylcholine receptor subtypes. FEBS Lett., 240, 95–100

    Google Scholar 

  • Bunzow, J. R., Van Tol, H. H. M., Grandy, D. K., Albert, P., Salon, J., Christie, M., Machida, C. A., Neve, K. A. and Civelli, O. (1988). Cloning and expression of a rat D2 dopamine receptor cDNA. Nature, 336, 783–787

    Google Scholar 

  • Burgen, A. S. V., Hiley, C. R. and Young, J. M. (1974). The binding of [3H]-propylbenzilylcholine mustard by longitudinal muscle strips from guinea-pig small intestine. Br. J. Pharmacol., 50, 145–151

    Google Scholar 

  • Buss, A. E., Mumby, S. M., Casey, P. J., Gilman, A. G. and Bartholomew, M. S. (1987). Myristolated α subunit of guanine nucleotide-binding regulatory proteins. Proc. Natl Acad. Sci. USA, 84, 7493–7497

    Google Scholar 

  • Carson, S. (1982). Cholate-salt solubilization of bovine brain muscarinic receptors. Biochem. Pharmacol., 31, 1806–1809

    Google Scholar 

  • Cassel, D. and Selinger, Z. (1978). Mechanism of adenylate cyclase activation through β-adrenergic receptor: Catecholamine-induced displacement of bound GDP by GTP. Proc. Natl Acad. Sci. USA, 75, 4155–4159

    Google Scholar 

  • Clark, A. J. (1926). The antagonism between acetylcholine and atropine. J. Physiol., 61, 547–556

    Google Scholar 

  • Clark, A. J. (1937). General Pharmacology, Julius Springer, Berlin Conklin, B. R., Brann, M. R., Buckley, N. J., Ma, A. L., Bonner, T. I. and Axelrod, J. (1988). Stimulation of arachidonic acid release and inhibition of mitogenesis by cloned genes for muscarinic receptor subtypes stably expressed in A9 L cells. Proc. Natl Acad. Sci. USA, 85, 8698–8702

    Google Scholar 

  • Cotecchia, S., Schwinn, D. A., Randall, R. R., Lefkowitz, R. J., Caron, M. G. and Kobilka, B. K. (1988). Molecular cloning and expression of the cDNA for the hamster α1-adrenergic receptor. Proc. Natl Acad. Sci. USA, 85, 7159–7163

    Google Scholar 

  • Curtis, C. A. M., Wheatley, M., Bansal, S., Birdsall, N. M. J., Eveleigh, P., Pedder, E. K., Poyner, D. and Hulme, E. C. (1989). Propylbenzilylcholine mustard labels an acidic residue in transmembrane helix 3 of the muscarinic receptor. J. Biol. Chem., 264, 489–495

    Google Scholar 

  • Dale, H. H. (1914). The action of certain esters and ethers of choline, and their relation to muscarine. J. Pharmacol. Exp. Ther., 6, 147–190

    Google Scholar 

  • Dayhoff, M. O., Schwartz, R. M. and Orcutt, B. C. (1978). A model of evolutionary change in proteins. In Atlas of Protein Sequence and Structure (ed. M. O. Dayhoff). National Biomedical Research Foundation, Silver Spring, Maryland, pp. 345–352

    Google Scholar 

  • Dixon, R. A. F., Sigal, I. S., Candelore, M. R., Register, R. B., Scattergood, W., Rands, E. and Strader, C. D. (1987). Structural features required for ligand binding to the β-adrenergic receptor. EMBO Jl, 6, 3269–3275

    Google Scholar 

  • Dohlman, H. G., Caron, M. G. and Lefkowitz, R. J. (1987). A family of receptors coupled to guanine nucleotide regulatory proteins. Biochemistry, 26, 2658–2664

    Google Scholar 

  • Ehlert, F. J. (1985). The relationship between muscarinic receptor occupancy and adenylate cyclase inhibition in the rabbit myocardium. Molec. Pharmacol., 28, 410–421

    Google Scholar 

  • Ehlert, F. J., Roeske, W. R., Rosenberger, L. B. and Yamamura, H. I. (1980). The influence of guanyl-5’-yl imidodiphosphate and sodium on muscarinic receptor binding in the rat brain and longitudinal muscle of the rat ileum. Life Sci., 26, 245–252

    Google Scholar 

  • Evans, T., Hepler, J. R., Masters, S. B., Brown, J. H. and Harden, T. K. (1985). Guanine nucleotide regulation of agonist binding to muscarinic cholinergic receptors. Biochem. J., 232, 751–757

    Google Scholar 

  • Fargin, A., Raymond, J. R., Lohse, M. J., Kobilka, B. K., Caron, M. G. and Lefkowitz, R. J. (1988). The genomic clone G-21 which resembles a β-adrenergic receptor sequence encodes the 5-HT1A receptor. Nature, 335, 358–360

    Google Scholar 

  • Ferguson, K. M., Higashijima, T., Smigel, M. D. and Gilman, A. G. (1986). The influence of bound GDP on the kinetics of guanine nucleotide binding to G proteins. J. Biol. Chem., 261, 7393–7399

    Google Scholar 

  • Findlay, J. B. C. and Pappin, D. J. C. (1986). The opsin family of proteins. Biochem. J., 238, 625–642

    Google Scholar 

  • Florio, V. A. and Sternweis, P. C. (1985). Reconstitution of resolved muscarinic cholinergic receptors with purified GTP-binding proteins. J. Biol. Chem., 260, 3477–3483

    Google Scholar 

  • Florio, V. A. and Sternweis, P. C. (1989). Mechanisms of muscarinic receptor action on Go in reconstituted phospholipid vesicles. J. Biol. Chem., 264, 3909–3915

    Google Scholar 

  • Fong, H. K. W., Yoshumoto, K. K., Eversole-Cire, P. and Simon, M. I. (1988). Identification of a GTP-binding protein α subunit that lacks an apparent ADP-ribosylation site for pertussis toxin. Proc. Natl Acad. Sci. USA, 85, 3066–3070

    Google Scholar 

  • Franke, R. R., Sakmar, T. P., Oprian, D. D. and Khorana, H. G. (1988). A single amino acid substitution in rhodopsin (lysine 248→leucine) prevents activation of transducin. J. Biol Chem., 263, 2119–2122

    Google Scholar 

  • Friedrich, T. and Burckhardt, G. (1988). Inhibition and labeling of the rat renal Na+/H+-exchanger by an antagonist of muscarinic acetylcholine receptors. FEBS Lett., 157, 921–929

    Google Scholar 

  • Frielle, T., Collins, S., Daniel, K. W., Caron, M. G., Lefkowitz, R. J. and Kobilka, B. K. (1987). Cloning of the cDNA for the human pradrenergic receptor. Proc. Natl Acad. Sci. USA, 84, 7920–7924

    Google Scholar 

  • Frielle, T., Daniel, K. W., Caron, M. G. and Lefkowitz, R. J. (1988). Structural basis of β-adrenergic receptor subtype specificity studied with chimeric β12-adrenergic receptors. Proc. Natl Acad. Sci. USA, 85, 9494–9498

    Google Scholar 

  • Fukuda, K., Higashida, H., Kubo, T., Maeda, A., Akiba, I., Bujo, H., Mishina, M. and Numa, S. (1988). Selective coupling with K+ currents of muscarinic acetylcholine receptor subtypes in NG 108–15 cells. Nature, 335, 355–358

    Google Scholar 

  • Fukuda, K., Kubo, T., Akiba, I., Maeda, A., Mishina, M. and Numa, S. (1987). Molecular distinction between muscarinic acetylcholine receptor subtypes. Nature, 327, 623–625

    Google Scholar 

  • Gaddum, J. H. (1937). The quanitative effects of antagonistic drugs. J. Physiol., 89, 7–9

    Google Scholar 

  • Gainer, M. W. and Nathanson, N. M. (1983). Properties of a solubilized guanyl nucleotide sensitive muscarinic acetylcholine receptor. Soc. Neurosci. Abstr., 13, 169

    Google Scholar 

  • Gautam, N., Baetscher, M., Aebersold, R. and Simon, M. I. (1989). A G protein gamma subunit shares homology with ras proteins. Science, N. Y., 244, 971–974

    Google Scholar 

  • Giachetti, A., Micheletti, R. and Montagna, E. (1986). Cardioselective profile of AF-DX 116, a novel muscarine M2 receptor antagonist. Life Sci., 38, 1663–1672

    Google Scholar 

  • Gill, E. W. and Rang, H. P. (1966). An alkylating derivative of benzilylcholine with specific and long-lasting parasympatholytic activity. Molec. Pharmacol., 2, 284–297

    Google Scholar 

  • Gilman, A. G. (1987). G proteins: transducers of receptor-generated signals. Ann. Rev. Biochem., 56, 615–649

    Google Scholar 

  • Haga, T. (1980). Molecular size of muscarinic acetylcholine receptors of rat brain. FEBS Lett., 113, 68–72

    Google Scholar 

  • Haga, T. (1989). The structure and function of muscarinic acetylcholine receptors. In Biosignal Transduction Mechanisms (ed. M. Kasai et al.). Japan Sci. Soc. Press, Tokyo/Springer-Verlag, Berlin, pp. 115–138

    Google Scholar 

  • Haga, K. and Haga, T. (1983). Affinity chromatography of the muscarinic acetylcholine receptor. J. Biol. Chem., 258, 13575–13579

    Google Scholar 

  • Haga, K. and Haga, T. (1985). Purification of the muscarinic acetylcholine receptor from porcine brain. J. Biol. Chem., 260, 7927–7935

    Google Scholar 

  • Haga, K. and Haga, T. (1989). Agonist-dependent phosphorylation of cerebral and atrial muscarinic receptors: blockade of the phosphorylation by G proteins and its reversal by guanine nucleotides. Biomed. Res., 10, 293–299

    Google Scholar 

  • Haga, T. and Haga, K. (1987a). Reconstitution of muscarinic cholinoceptors and GTP-binding proteins from porcine brain. In Cellular and Molecular Basis of Cholinergic Function (ed. M. J. Dowdall and J. N. Hawthorne). Ellis Horwood, Chichester, and VCH, Weinheim, pp. 104–115

    Google Scholar 

  • Haga, T. and Haga, K. (1987b). Interaction of the muscarinic acetylcholine receptor and GTP-binding proteins. Biomed. Res., 8, 149–156

    Google Scholar 

  • Haga, T., Haga, K., Berstein, G., Nishiyama, T., Uchiyama, H. and Ichiyama, A. (1988). Molecular properties of muscarinic receptors. Trends Pharmacol. Sci. Suppl.: Subtypes of Muscarinic Receptors III, 12–18

    Google Scholar 

  • Haga, K., Haga, T. and Ichiyama, A. (1986). 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). J. Biol. Chem., 261, 10133–10140

    Google Scholar 

  • Haga, K., Haga, T., Ichiyama, A., Katada, T., Kurose, H. and Ui, M. (1985). Functional reconstitution of purified muscarinic receptors and inhibitory guanine nucleotide regulatory protein. Nature, 316, 731–733

    Google Scholar 

  • Haga, T., Nukada, T. and Haga, K. (1982). Solubilization of the muscarinic acetylcholine receptor by sodium cholate: stabilization of the receptor by muscarinic ligands. Biomed. Res., 3, 695–698

    Google Scholar 

  • Haga, K., Uchiyama, H., Haga, T., Ichiyama, A., Kangawa, K. and Matsuo, H. (1989). Cerebral muscarinic acetylcholine receptors interact with three kinds of GTP-binding proteins in a reconstitution system of purified components. Molec. Pharmacol., 35, 286–294

    Google Scholar 

  • Hammer,R.,Berrie,C.P., Birdsall, N.J.M.,Burgen, A.S.V. andHulme, E.C. (1980). Pirenzepine distinguishes between different subclasses of muscarinic receptors. Nature, 283, 90–92

    Google Scholar 

  • Hammer, R. and Giachetti, A. (1982). Muscarinic receptor subtypes: Ml and M2 biochemical and functional characterization. Life Sci., 31, 2991–2998

    Google Scholar 

  • Hammer, R., Giraldo, E., Schiavi, G. B., Monferini, E. and Ladinsky, H. (1986). Binding profile of a novel cardioselective muscarine receptor antagonist, AF-DX 116, to membranes of peripheral tissues and brain in the rat. Life Sci., 38, 1653–1662

    Google Scholar 

  • Herron, C. S. and Schimerlik, M. I. (1983). Glycoprotein properties of the solubilized atrial muscarinic acetylcholine receptor. J. Neurochem., 41, 1414–1420

    Google Scholar 

  • Ho, A. K. S., Ling, Q.-L., Duffield, R., Lam, P. H. and Wang, J. H. (1987). Phosphorylation of brain muscarinic receptor: evidence of receptor regulation. Biochem. Biophys. Res. Commun., 142, 911–918

    Google Scholar 

  • Hubbard, S. C. and Ivatt, R. J. (1981). Synthesis and processing of asparagine-linked oligosaccharides. Ann. Rev. Biochem., 50, 555–583

    Google Scholar 

  • Hulme, E. C., Berrie, C. P., Birdsall, N. J. M., Jameson, M. and Stockton, J. M. (1983). Regulation of muscarinic agonist binding by cations and guanine nucleotides. Eur. J. Pharmacol., 94, 59–72

    Google Scholar 

  • Hulme, E. C., Birdsall, N. J. M., Burgen, A. S. V. and Mehta, P. (1978). The binding of antagonists to brain muscarinic receptors. Molec. Pharmacol., 14, 737–750

    Google Scholar 

  • Jackson, T. R., Blair, L. A. C., Marshall, J., Goedert, M. and Hanley, M. R. (1988). The mas oncogene encodes an angiotensin receptor. Nature, 335, 437–440

    Google Scholar 

  • Jones, D. T. and Reed, R. R. (1987). Molecular cloning of five GTP-binding protein cDNA species from rat olfactory neuroepithelium. J. Biol. Chem., 262, 14241–14249

    Google Scholar 

  • Jones, S. V. P., Barker, J. L., Bonner, T. I., Buckley, N. J. and Brann, M. B. (1988a). Electrophysiological characterization of cloned ml muscarinic receptors expressed in A9 L cells. Proc. Natl Acad. Sci. USA, 85, 4056–4060

    Google Scholar 

  • Jones, S. V. P., Barker, J. L., Buckley, N. J., Bonner, T. I., Collins, R. M. and Brann, M. B. (1988b). Cloned muscarinic receptor subtypes expressed in A9 L cells differ in their coupling to electrical responses. Molec. Pharmacol., 34, 421–426

    Google Scholar 

  • Julius, D., MacDermott, A. B., Axel, R. and Jessel, T. M. (1988). Molecular characterization of a functional cDNA encoding the serotonin lc receptor. Science, N.Y., 241, 558–564

    Google Scholar 

  • Karnik, S. S., Sakmar, T. P., Chen, H.-B. and Khorana, H. G. (1988). Cysteine residues 110 and 187 are essential for the formation of correct structure in bovine rhodopsin. J. Biol. Chem., 85, 8459–8463

    Google Scholar 

  • Katada, T., Oinuma, M., Kusakabe, K. and Ui, M. (1987). A new GTP-binding protein in brain tissues serving as the specific substrate of islet-activating protein, pertussis toxin. FEBS Lett., 213, 85–89

    Google Scholar 

  • Khorana, H. G. (1988). Bacteriorhodopsin, a membrane protein that uses light to translocate protons. J. Biol. Chem., 263, 7439–7442

    Google Scholar 

  • Kobilka, B. K., Dixon, R. A. F., Frielle, T., Dohlman, H. G., Bolanowski, M. A., Sigal, I. S., Yang-Feng, T. L., Francke, U., Caron, M. G. and Lefkowitz, R. J. (1987a). cDNA for the human β2-adrenergic receptor: a protein with multiple membrane-spanning domains and encoded by a gene whose chromosomal location is shared with that of the receptor for the platelet-derived growth factor. Proc. Natl Acad. Sci. USA, 84, 46–50

    Google Scholar 

  • Kobilka, B. K., Frielle, T., Collins, S., Yang-Feng, T., Kobilka, T. S., Francke, U., Lefkowitz, R. J. and Caron, M. G. (1987c). An intronless gene encoding a potential member of the family of receptors coupled to guanine nucleotide regulatory proteins. Nature, 329, 76–79

    Google Scholar 

  • Kobilka, B. K., Kobilka, T. S., Daniel, K., Regan, J. W., Caron, M. G. and Lefkowitz, R. J. (1988). Chimeric α2-, β2-adrenergic receptors: delineation of domains involved in effector coupling and ligand binding specificity. Science, N.Y., 240, 1310–1316

    Google Scholar 

  • Kobilka, B. K., Matsui, H., Kobilka, T. S., Yang-Feng, T. L., Francke, Y., Caron, M. G., Lefkowitz, R. J. and Regan, J. W. (1987b). Cloning, sequencing, and expression of the gene coding for the human platelet α2-adrenergic receptor. Science, N. Y., 238, 650–656

    Google Scholar 

  • Kozasa, T., Itoh, H., Tsukamoto, T. and Kaziro, Y. (1988) Isolation and characterization of the human Gsa gene. Proc. Natl Acad. Sci. USA, 85, 2081–2085.

    Google Scholar 

  • Kubo, T., Bujo, H., Akiba, I., Nakai, J., Mishina, M. and Numa, S. (1988). Location of a region of the muscarinic acetylcholine receptor involved in selective effector coupling. FEBS Lett., 241, 119–125

    Google Scholar 

  • Kubo, T., Fukuda, K., Mikami, A., Maeda, A., Takahashi, H., Mishina, M., Haga, T., Haga, K., Ichiyama, A., Kangawa, K., Kojima, M., Matsuo, H., Hirose, T. and Numa, S. (1986a). Cloning, sequencing and expression of complementary DNA encoding the muscarinic acetylcholine receptor. Nature, 323, 411–416

    Google Scholar 

  • Kubo, T., Maeda, A., Sugimoto, K, Akiba, I., Mikami, A., Takahashi, H., Haga, T., Haga, K., Ichiyama, A., Kangawa, K., Matsuo, H., Hirose, T. and Numa, S. (1986b). Primary structure of porcine cardiac muscarinic acetylcholine receptor deduced from the cDNA sequence. FEBS Lett., 209, 367–372

    Google Scholar 

  • Kuhn, H., Hall, S. W. and Widen, U. (1984). Light-induced binding of 48-kDa protein to photoreceptor membranes is highly enhanced by phosphorylation of rhodopsin. FEBS Lett., 176, 473–478

    Google Scholar 

  • Kurose, H., Katada, T., Haga, K., Haga, T., Ichiyama, A. and Ui, M. (1986). Functional reconstitution of purified muscarinic receptors with inhibitory guanine nucleotide regulatory protein reconstituted in phospholipid vesicles. J. Biol. Chem., 261, 6423–6428

    Google Scholar 

  • Kwatra, M. M. and Hosey, M. M. (1986). Phosphorylation of the cardiac muscarinic receptor in intact chick heart and its regulation by a muscarinic agonist. J. Biol. Chem., 261, 14429–14432

    Google Scholar 

  • Kwatra, M. M., Leung, E., Maan, A. C., McMahon, K. K. Ptasienski, J., Green, R. D. and Hosey, M. M. (1987). Correlation of agonist-induced phosphorylation of chick heart muscarinic receptors with receptor desensitization. J. Biol. Chem., 262, 16314–16321

    Google Scholar 

  • Kwatra, M. M., Benovic, J. L., Caron, M. G., Lefkowitz, R. J. and Hosey, M. M. (1989a). Phosphorylation of chick heart muscarinic cholinergic receptors by the β-adrenergic receptor kinase. Biochemistry, 28, 4543–4547

    Google Scholar 

  • Kwatra, M. M., Ptasienski, J. and Hosey, M. M. (1989b). The porcine heart M2 muscarinic receptor: agonist-induced phosphorylation and comparison of properties with the chick heart receptor. Molec. Pharmacol., 35, 553–558

    Google Scholar 

  • Kyte, J. and Doolittle, R. F. (1982). A simple method for displaying the hydropathic character of a protein. J. Molec. Biol., 157, 105–132

    Google Scholar 

  • Ladinsky, H., Giraldo, E., Monferini, E., Schiavi, G. B., Vigan, M. A., De Conti, L., Micheletti, R. and Hammer, R. (1988). Muscarinic receptor heterogeneity in smooth muscle: binding and functional studies with AF-DX 116. Trends Pharmacol. Sci. Suppl.: Subtypes of Muscarinic Receptors III, 44 48

    Google Scholar 

  • Laduron, P. M., Verwimp, M. and Leysen, J. E. (1979). Stereospecific in vitro binding of [3H]-dexetimide to brain muscarinic receptors. J. Neurochem., 32, 421–427

    Google Scholar 

  • Lai, J., Mei, L., Roeske, W. R., Chung, F.-Z., Yamamura, H. I. and Venter, J. C. (1988). The cloned murine M1 muscarinic receptor is associated with the hydrolysis of phosphatidylinositols in transfected murine B82 cells. Life Sci., 42, 2489–2502

    Google Scholar 

  • Lambrecht, G., Moser, U., Wagner, M., Wess, J., Gmelin, G., Raseiner, K., Strohmann, C., Tacke, R. and Mutschler, E. (1988). Pharmacological and electrophysiological evidence for muscarinic M1 and M2 receptor heterogeneity. Trends Pharmacol Sci. Suppl.: Subtypes of Muscarinic Receptors III, 82

    Google Scholar 

  • Lefkowitz, R. J., Stadel, J. M. and Caron, M. C. (1983). Adenylate cyclase-coupled beta-adrenergic receptors: structure and mechanisms of activation and desensitization. Ann. Rev. Biochem., 52, 159–186

    Google Scholar 

  • Liang, M., Martin, M. W. and Harden, T. K. (1987). [3H]-Propylbenzilylcholine mustard-labeling of muscarinic cholinergic receptors that selectively couple to phospholipase C or adenylate cyclase in two cultured cell lines. Molec. Pharmacol., 32, 443–449

    Google Scholar 

  • Liao, C.-F., Themmen, A. P. N., Joho, R., Barberis, C., Birnbaumer, M. and Birnbaumer, L. (1989). Molecular cloning and expression of a fifth muscarinic acetylcholine receptor. J. Biol. Chem., 264, 7328–7337

    Google Scholar 

  • Liles, W. C., Hunter, D. D., Meier, K. E. and Nathanson, N. M. (1986). Activation of protein kinase C induces rapid internalization and subsequent degradation of muscarinic acetylcholine receptors in neuroblastoma cells. J. Biol. Chem., 261, 5307–5313

    Google Scholar 

  • Liles, W. C. and Nathanson, N. M. (1986). Regulation of neuronal muscarinic acetylcholine receptor number by protein glycosylation. J. Neurochem., 46, 89–95

    Google Scholar 

  • Loewi, O. (1921). Uber humorale Ubertragbarkeit der Herznervenwirkung. Pflügers Arch. Gesamte Physiol., 189, 239–242

    Google Scholar 

  • Loewi, O. and Navratil, E. (1926). Uber humorale Ubertragbarkeit der Herznervenwirkung. X. Mitteilung. Uber das Schiksal des Vagustoff. Pflügers Arch. Gesamte Physiol., 214, 678–688

    Google Scholar 

  • Luthin, G. R. and Wolfe, B. B. (1985). Characterization of [3H]-pirenzepine binding to muscarinic cholinergic receptors solubilized from rat brain. J. Pharmacol. Expl Ther., 234, 37–44

    Google Scholar 

  • McArdle, H., Mullaney, I., Magee, A., Unson, C. and Milligan, G. (1988). GTP analogues cause release of the alpha subunit of the GTP binding protein, G0, from the plasma membrane of NG 108–15 cells. Biochem. Biophys. Res. Comm., 152, 243–251

    Google Scholar 

  • Maeda, A., Kubo, T., Mishina, M. and Numa, S. (1988). Tissue distribution of mRNAs encoding muscarinic acetylcholine receptor subtypes. FEBS Lett., 239, 339–342

    Google Scholar 

  • Masu, Y., Nakayama, K., Tamaki, H., Harada, Y., Kuno, M. and Nakanishi, S. (1987). cDNA cloning of bovine substance-K receptor through oocyte expression system. Nature, 329, 836–838

    Google Scholar 

  • Matsuoka, M., Itoh, H., Kozasa, T. and Kaziro, Y. (1988). Sequence analysis of cDNA and genomic DNA for a putative pertussis toxin-insensitive guanine nucleotide-binding regulatory protein a subunit. Proc. Natl Acad. Sci. USA, 85, 5384–5388

    Google Scholar 

  • Mei, L., Wang, J.-X., Roeske, W. R. and Yamamura, H. I. (1987). Thermodynamic analyses of pirenzepine binding to membrane-bound and solubilized muscarinic receptors from rat forebrain and heart. J. Pharmacol. Expl Ther., 242, 991–1000

    Google Scholar 

  • Melchiorre, C., Angeli, P., Lambrecht, G., Mutschler, E., Picchio, M. T. and Wess, J. (1987). Antimuscarinic action of methoctramine, a new cardioselective M-2 muscarinic receptor antagonist, alone and in combination with atropine and gallamine. Eur. J. Pharmacol., 144, 117–124

    Google Scholar 

  • Milligan, G., Mullaney, I., Unson, C., Marshall, L., Spiegel, A. and McArdle, H. (1988). GTP analogues promote release of the α subunit of the guanine nucleotide binding protein, G12, from membranes of rat glioma C6 BU1 cells. Biochem. J., 254, 391–396

    Google Scholar 

  • Mizushima, A., Uchida, S., Zhou, X.-M., Kagiya, T. and Yoshida, H. (1987). Cardiac M2 receptors consist of two different types, both regulated by GTP. Eur. J. Pharmacol., 135, 403–409

    Google Scholar 

  • Murayama, T. and Ui, M. (1983). Loss of the inhibitory function of the guanine nucleotide-regulatory component of the adenylate cyclase due to its ADP-ribosylation by islet-activating protein, pertussis toxin, in adipocyte membranes. J. Biol. Chem., 258, 3319–3326

    Google Scholar 

  • Mutschler, E., Gmelin, G., Moser, U., Wess, J. and Lambrecht, G. (1987). Structure-activity relationships of drugs acting selectively at different muscarinic receptors. In Pharmacology, International Congress Series No. 750 (ed. M. J. Rand and C. Raper), Elsevier, Amsterdam, pp. 67–75

    Google Scholar 

  • Nathans, J. and Hogness, D. S. (1984). Isolation and nucleotide sequence of the gene encoding human rhodopsin. Proc. Natl Acad. Sci. USA, 81, 4851–855

    Google Scholar 

  • Nathanson, N. M. (1987). Molecular properties of the muscarinic acetylcholine receptor. Ann. Rev. Neurosci., 10, 195–236

    Google Scholar 

  • Neher, E., Marty, A., Fukuda, K., Kubo, T. and Numa, S. (1988). Intracellular calcium release mediated by two muscarinic receptor subtypes. FEBS Lett., 240, 88–94

    Google Scholar 

  • Nishiyama, T., Berstein, G., Ikegaya, T., Haga, T., Ichiyama, A., Kobayashi, A. and Yamazaki, N. (1989). Comparison between purified cerebral and atrial muscarinic acetylcholine receptors: pirenzepine binding and the effect of sulfhydryl reagents. Biomed. Res., 10, 251–260

    Google Scholar 

  • Nukada, T., Haga, T. and Ichiyama, A. (1983a). Muscarinic receptors in porcine caudate nucleus. I. Enhancement by nickel and other cations of [3H]-cis-methyldioxolane binding to guanyl nucleotide-sensitive sites. Molec. Pharmacol., 24, 366–373

    Google Scholar 

  • Nukada, T., Haga, T. and Ichiyama, A. (1983b). Muscarinic receptors in porcine caudate nucleus. II. Different effects of N-ethylmaleimide on [3H]-cis-methyldioxolane binding to heat-labile (guanyl nucleotide-sensitive) sites and heat-stable (guanyl nucleotide-insensitive) sites. Molec. Pharmacol., 24, 374–379

    Google Scholar 

  • Nunnari, J. M., Repaske, M. G., Brandon, S., Cragoe, E. J. and Limbird, L. E. (1987). Regulation of porcine brain α2-adrenergic receptor by Na+, H+, and inhibitors of Na+, H+, exchange. J. Biol. Chem., 262, 12387–12392

    Google Scholar 

  • O’Dowd, B. F., Hnatowitch, M., Regan, J. W., Leader, W. M., Caron, M. G. and Lefkowitz, R. J. (1988). Site-directed mutagenesis of the cytoplasmic domains of the humanv β2-adrenergic receptor. Localization of regions involved in G protein-receptor coupling. J. Biol. Chem., 31, 15985–15992

    Google Scholar 

  • Ovchinnikov, Y. A. (1982). Rhodopsin and bacteriorhodopsin: structure-function relationships. FEBS Lett., 148, 179–191

    Google Scholar 

  • Parascandola, J. (1981). Origins of the receptor theory. In Towards Understanding Receptors (ed. J. W. Lamble), Elsevier, Amsterdam, pp. 1–7

    Google Scholar 

  • Paton, W. D. M. and Rang, H. P. (1965). The uptake of atropine and related drugs by intestinal smooth muscle of the guinea pig in relation to acetylcholine receptors. Proc. R. Soc. Lond., Ser. B, 163, 1–44

    Google Scholar 

  • Peralta, E. G., Ashkenazi, A., Winslow, J. W., Ramachandran, J. and Capon, D. J. (1988b). Differential regulation of PI hydrolysis and adenylyl cyclase by muscarinic receptor subtypes. Nature, 334, 434–437

    Google Scholar 

  • Peralta, E. G., Ashkenazi, A., Winslow, J. W., Smith, D. H., Ramachandran, J. and Capon, D. J. (1987b). Distinct primary structures, ligand-binding properties and tissue-specific expression of four human muscarinic acetylcholine receptors. EMBO Jl, 6, 3923–3929

    Google Scholar 

  • Peralta, E. G., Winslow, J. W., Ashkenazi, A., Smith, D. H., Ramachandran, J. and Capon, D. J. (1988a). Structural basis of mascarinic acetylcholine receptor subtype diversity. Trends Pharmacol. Sci. Suppl.: Subtypes of Muscarinic Receptors III, 6–11

    Google Scholar 

  • Peralta, E. G., Winslow, J. W., Peterson, G. L., Smith, D. H., Ashkenazi, A., Ramachandran, J., Schimerlik, M. I. and Capon, D. J. (1987a). Primary structure and biochemical properties of an M2 muscarinic receptor. Science, N. Y., 236, 600–605

    Google Scholar 

  • Peterson, G. L., Herron, G. S., Yamaki, M., Fullerton, D. S. and Schimerlik, M. I. (1984). Purification of the muscarinic acetylcholine receptor from porcine atria. Proc. Natl Acad. Sci. USA, 81, 4993–4997

    Google Scholar 

  • Peterson, G. L., Rosenbaum, L. C., Broderick, D. J. and Schimerlik, M. I. (1986). Physical properties of the purified cardiac muscarinic acetylcholine receptor. Biochemistry, 25, 3189–3202

    Google Scholar 

  • Peterson, G. L., Rosenbaum, L. C. and Schimerlik, M. I. (1988). Solubilization and hydrodynamic properties of pig atrial muscarinic acetylcholine receptor in dodecyl β-D-maltoside. Biochem. J., 255, 553–560

    Google Scholar 

  • Pinkas-Kramarski, R., Stein, R., Zimmer, Y. and Sokolovsky, M. (1988). Cloned rat M3 muscarinic receptors mediate phosphoinositide hydrolysis but not adenylate cyclase inhibition. FEBS Lett., 239, 174–178

    Google Scholar 

  • Regan, J. W. Kobilka, T. S., Yang-Feng, T. L., Caron, M. G., Lefkowitz, R. J. and Kobilka, B. K. (1988). Cloning and expression of a human kidney cDNA for an α2-adrenergic receptor subtype. Proc. Natl Acad. Sci. USA, 85, 6301–6305

    Google Scholar 

  • Rosenbaum, L. C., Malencik, D. A., Anderson, S. R., Tota, M. R. and Schimerlik, M. I. (1987). Phosphorylation of the porcine atrial muscarinic acetylcholine receptor by cyclic AMP dependent protein kinase. Biochemistry, 26, 8183–8188

    Google Scholar 

  • Ross, E. M. and Gilman, A. G. (1980). Biochemical properties of hormone-sensitive adenylate cyclase. Ann. Rev. Biochem., 49, 533–564

    Google Scholar 

  • Rües, K.-P. and Liefländer, M. (1979). Action of detergents on covalently labelled, membrane bound muscarinic acetylcholine receptor of bovine nucleus caudatus. Biochem. Biophys. Res. Commun., 88, 627–633

    Google Scholar 

  • Schimerlik, M. I. (1989). Structure and regulation of muscarinic receptors. Ann. Rev. Physiol., 51, 217–227

    Google Scholar 

  • Schimerlik, M. L, Miller, S., Peterson, G. L., Rosenbaum, L. C. and Tota, M. R. (1986). Biochemical studies on muscarinic receptors in porcine atrium. Trends Pharmacol. Sci. Suppl.: Subtypes of Muscarinic Receptors II, 2–7

    Google Scholar 

  • Shapiro, R. A., Scherer, N. M., Habecker, B. A., Subers, E. M. and Nathanson, N. M. (1988). Isolation, sequence, and functional expression of the mouse Ml muscarinic acetylcholine receptor gene. J. Biol. Chem., 263, 18397–18403

    Google Scholar 

  • Shirakawa, O., Kuno, T. and Tanaka, C. (1983). The glycoprotein nature of solubilized muscarinic acetylcholine receptors from bovine cerebral cortex. Biochem. Biophys. Res. Commun., 115, 814–819

    Google Scholar 

  • Sokolovsky, M., Gurwitz, D. and Galron, R. (1980). Muscarinic receptor binding in mouse brain: regulation by guanine nucleotides. Biochem. Biophys. Res. Commun., 94, 487–492

    Google Scholar 

  • Stein, R., Pinkas-Kramarski, R. and Sokolovsky, M. (1988). Cloned Ml muscarinic receptors mediate both adenylate cyclase inhibition and phosphoinositide turnover. EMBO Jl, 7, 3031–3035

    Google Scholar 

  • Sternweis, P. C. (1986). The purified subunits of Go and Gi from bovine brain require βγ for association with phospholipid vesicles. J. Biol. Chem., 261, 631–637

    Google Scholar 

  • Sternweis, P. C. and Robishaw, J. D. (1984). Isolation of two proteins with high affinity for guanine nucleotides from membranes of bovine brain. J. Biol. Chem., 259, 3586–3595

    Google Scholar 

  • Strader, C. D., Dixon, R. A. F., Cheung, A. H., Candelore, M. R., Blake, A. D. and Sigal, I. S. (1987). Conserved aspartic acid residues 79 and 113 of the β-adrenergic receptor have different roles in receptor function. J. Biol. Chem., 262, 16439–16443

    Google Scholar 

  • Strader, C. D., Sigal, I. S., Candelore, M. R., Rands, E., Hill, W. and Dixon, R. A. F. (1988).

    Google Scholar 

  • Conserved aspartic acid residues 79 and 113 of the p-adrenergic receptor have different roles in receptor function. J. Biol. Chem., 263, 10267–10271

    Google Scholar 

  • Stryer, L. (1986). Cyclic GMP cascade of vision. Ann. Rev. Neurosci., 9, 87–119

    Google Scholar 

  • Tota, M. R., Kahler, K. R. and Schimerlik, M. I. (1987). Reconstitution of the purified porcine atrial muscarinic acetylcholine receptor with purified porcine atrial inhibitory guanine nucleotide binding protein. Biochemistry, 26, 8175–8182

    Google Scholar 

  • Uchida, S., Matsumoto, K., Mizushima, A., Osugi, T., Higuchi, H. and Yoshida, H. (1984). Effects of guanine nucleotide and sulfhydryl reagent on subpopulations of muscarinic acetylcholine receptors in mammalian hearts: possible evidence for interconversion of super-high and low affinity agonist binding sites. Eur. J. Pharmacol., 100, 291–298

    Google Scholar 

  • Vauquelin, G., André C., De Backer, J.-P., Laduron, P. and Strosberg, A. D. (1982). Agonist-mediated conformational changes of muscarinic receptors in rat brain. Eur. J. Biochem., 125, 117–124

    Google Scholar 

  • Wang, J.-X., Mei, L., Yamamura, H. I. and Roeske, W. R. (1987b). Solubilization with digitonin alters the kinetics of pirenzepine binding to muscarinic receptors from rat forebrain and heart. J. Pharmacol. Exp. Ther, 242, 981–990

    Google Scholar 

  • Wang, J.-X., Roeske, W. R., Gulya, K., Wang, W. and Yamamura, H. I. (1987a). [3H]-AF-DX 116 label subsets of muscarinic acetylcholine receptors in rat brain and heart. Life Sci., 41, 1751–1760

    Google Scholar 

  • Watson, M., Yamamura, H. I. and Roeske, W. R. (1983). A unique regulatory profile and regional distribution of [3H]-pirenzepine binding in the rat provide evidence for distinct M1 and M2 muscarinic receptor subtypes. Life Sci., 32, 3001–3011

    Google Scholar 

  • Weiner, N. and Taylor, P. (1985). Neurohormonal transmission: the autonomic and somatic motor nervous system. In The Pharmacological Basis of Therapeutics (ed. A. G. Gilman, L. S. Goodman, T. W. Rall and F. Murad), Macmillan, New York, pp. 66–99

    Google Scholar 

  • Wheatley, M., Birdsall, N. J. M., Curtis, C., Eveleigh, P., Pedder, E. K., Poyner, D., Stockton, J. M. and Hulme, E. C. (1987). The structure and properties of the purified muscarinic acetylcholine receptor from rat forebrain. Trans. Biochem. Soc., 15, 113–116

    Google Scholar 

  • Wong, S. K.-F., Slaughter, C., Ruoho, A. and Ross, E. M. (1988). The catecholamine binding site of the β-adrenergic receptor is formed by juxtaposed membrane-spanning domains. J. Biol. Chem., 263, 7925–7928

    Google Scholar 

  • Yagisawa, H., Yamagishi, S. and Sugiyama, H. (1983). Characterization of muscarinic acetylcholine receptors as glycoproteins. Proc. Japan Acad., 59B, 324–327

    Google Scholar 

  • Yamamura, H. I. and Snyder, S. H. (1974). Muscarinic cholinergic binding in rat brain. Proc. Natl Acad. Sci. USA, 71, 1725–1729

    Google Scholar 

  • Young, D., Waitches, G., Birchmeier, C., Fasano, O. and Wigler, M. (1986). Isolation and characterization of a new cellular oncogene encoding a protein with multiple potential transmembrane domains. Cell, 45 711–719285-309

    Google Scholar 

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Berstein, G., Haga, T. (1990). Molecular Aspects of Muscarinic Receptors. In: Osborne, N.N. (eds) Current Aspects of the Neurosciences. Palgrave, London. https://doi.org/10.1007/978-1-349-10997-5_8

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