The Molecular Properties of the M1 Muscarinic Receptor and its Regulation of Cytosolic Calcium in a Eukaryotic Gene Expression System

  • Josephine Lai
  • Thomas L. Smith
  • Lin Mei
  • Masaaki Ikeda
  • Yutaka Fujiwara
  • Jorge Gomez
  • Marilyn Halonen
  • William R. Roeske
  • Henry I. Yamamura
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 287)

Abstract

Muscarinic receptor heterogeneity has been implicated in the selective binding characteristics of non-classical muscarinic antagonists such as pirenzepine (PZ) and AF-DX 116 (ll-[[2-[(diethyl-amino)methyl]-l-piperi-dinyl]acetyl]-5,ll-dihydro-6H-pyrido [2,3-b]-[l,4]benzodiazepine-6-one) (Watson et al., 1986). Pirenzepine labels a class of muscarinic receptor binding sites with high affinity, termed the Mi type, which is predominant in the brain. AF-DX 116, on the other hand, distinguishes a second class of binding sites by its high affinity, known as the M2 type, which is predominant in cardiac tissues (Giachetti et al., 1986). A third class of muscarinic receptor sites, noted for its low affinity for both PZ and AF-DX 116, is represented in a number of glandular tissues (Hammer et al., 1986; Korc et al., 1987). The heterogeneity of the muscarinic receptors was proven unequivocally by the identification of several genes (mi-m5, genotypic definition established by Bonner et al., 1987, 1988) which encode distinct polypeptides that show muscarinic cholinergic receptor properties (Bonner et al., 1987, 1988; Peralta et al., 1987; Liao et al., 1989). These structurally distinct types of the muscarinic receptors could be individually analyzed, by means of in vitro expression in eukaryotic cell lines, in order to correlate the structural diversity of the muscarinic receptors with their multiple physiological activities.

Keywords

Hydrolysis Electrophoresis Polypeptide Catecholamine Ampicillin 

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References

  1. 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.PubMedCrossRefGoogle Scholar
  2. 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 238:672–675.PubMedCrossRefGoogle Scholar
  3. Audigier, S.M.P., Wang, J.K.T. and Greengard, P., 1988, Membrane depolarization and carbamoyl choline stimulate phosphatidyl inositol turnover in intact nerve terminals. Proc. Natl. Acad. Sci. 85:2859–2863.PubMedCrossRefGoogle Scholar
  4. Berridge, M.J. and Irvine, R.F., 1984, Inositol phosphate, a novel second messenger in cellular signal transduction. Nature 312:315–321.PubMedCrossRefGoogle Scholar
  5. Berstein, G., Haga, T. and Ichiyama, A., 1989, Effect of the lipid environment on the differenial affinity of purified cerebral and atrial muscarinic acetylcholine receptors for pirenzepine. Mol. Pharmacol. 36:601–607.PubMedGoogle Scholar
  6. Bonner, T.I., Buckley, N.J., Young, A.C. and Brann, M.R., 1987, Identification of a family of muscarinic acetylcholine receptor genes. Science 237:527–532.PubMedCrossRefGoogle Scholar
  7. 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.PubMedCrossRefGoogle Scholar
  8. Brann, M.R., Buckley, N.J. and Bonner, T.I., 1988, The striatum and cerebral cortex express different muscarinic receptor mRNAs. FEBS lett. 230:90–94.PubMedCrossRefGoogle Scholar
  9. Buckley, N.J., Bonner, T.I., Buckley, C.M. and Brann, M.R., 1989, Antagonist binding properties of five cloned muscarinic receptors expressed in CH0-K1 cells. Mol. Pharmacol. 35:469–476.PubMedGoogle Scholar
  10. 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.PubMedCrossRefGoogle Scholar
  11. Burgen, A.S.Y., Hiley, C.R. and Young, J.M., 1974, The properties of muscarinic receptors in mammalian cerebral cortex. Br. J. Pharmacol. 51:279–285.PubMedGoogle Scholar
  12. 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 A9L cells. Proc. Natl. Acad. Sci. (U.S.A.) 85:8698–8702.CrossRefGoogle Scholar
  13. Curtis, C.A.M., Wheatley, M., Bansal, S., Birdsall, N.J.M., 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.PubMedGoogle Scholar
  14. Dadi, H.K. and Morris, R.J., 1984, Muscarinic cholinergic receptor of rat brain: factors influencing migration in electrophoresis and gel filtration in sodium dodecyl sulphate. Eur. J. Biochem. 144:617–628.PubMedCrossRefGoogle Scholar
  15. Diamant, S., Lev-Ari, I., Uzielli, I. and Atlas, D., 1988, Muscarinic agonists evoke neurotransmitter release: possible roles for phosphatidyl inositol bisphosphate breakdown products in neuromodulation. J. Neurochem. 51:795–802.PubMedCrossRefGoogle Scholar
  16. Earle, W.R., 1943, Production of malignancy in vitro; mouse fibroblast cultures and changes seen in living cells. J. Natl. Cancer Inst. 4:165–212.Google Scholar
  17. Ehrlich, B.E. and Watras, J., 1988, Inositol 1,4,5-trisphosphate activates a channel from smooth muscle sarcoplasmic reticulum. Nature 336:583–586.PubMedCrossRefGoogle Scholar
  18. Fisher, S.K., Domask, L.M. and Roland, R.M., 1989, Muscarinic receptor regulation of cytoplasmic Ca2+ concentrations in human SK-N-SH neuroblastoma cells: Ca2+ requirements for phospholipase C activation. Mol. Pharmacol. 35:195–204.PubMedGoogle Scholar
  19. 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.PubMedCrossRefGoogle Scholar
  20. 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.PubMedCrossRefGoogle Scholar
  21. Giachetti, A., Micheletti, R. and Montagna, E., 1986, Cardioselective profile of AF-DX 116, a muscarinic M2 receptor antagonist. Life Sci. 38:1663–1672.PubMedCrossRefGoogle Scholar
  22. Graham, F. and Van Der Eb, A., 1973, A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology 52:456–467.PubMedCrossRefGoogle Scholar
  23. Gunning, P., Leavitt, J., Muscat, G., Ng, S.Y. and Kecles, L., 1987, A human β-actin expression vector system directs high-level accumulation of antisense transcripts. Proc. Natl. Acad. Sci. (U.S.A.), 84:4831–4835.CrossRefGoogle Scholar
  24. Haga, T., 1980, Molecular size of muscarinic acetylcholine receptors of rat brain. FEBS lett. 113:68–72.PubMedCrossRefGoogle Scholar
  25. Haga, K. and Haga, T., 1985, Purification of the muscarinic acetylcholine receptor from porcine brain. J. Biol. Chem. 260:7927–7935.PubMedGoogle Scholar
  26. Hammer, R., Giraldo, E., Schiavi, G.B., Monferini, E. and Ladinsky, H., 1986, Binding profile of a novel cardioselective muscarinic receptor antagonist, AF-DX 116, to membranes of peripheral tissues and brain in the rat. Life Sci. 38:1657–1662.CrossRefGoogle Scholar
  27. Henquin, J.C., Garcia, M.C., Bozem, M., Hermans, M.P. and Nenquin, M., 1988, Muscarinic control of pancreatic B cell function involves sodium dependent depolarization and calcium influx. Endocrinology 122:2134–2142.PubMedCrossRefGoogle Scholar
  28. Inoue, K. and Kenimer, J.G., 1988, Muscarinic stimulation of calcium influx and norepinephrine release in PC12 cells. J. Biol. Chem. 263:8157–8161.PubMedGoogle Scholar
  29. Jones, S.V.P., Barker, J.L., Buckley, N.J., Bonner, T.I., Collins, R.M. and Brann, M.R., 1988, Electrophysiological characterization of cloned m1 muscarinic receptors expressed in A9L cells. Mol. Pharmacol. 34:421–426.PubMedGoogle Scholar
  30. Komulainen, H. and Bondy, S.C., 1987, The estimation of free calcium within synaptosomes and mitochondria with fura-2; comparison to quin-2. Neurochem. Int. 10:55–64.PubMedCrossRefGoogle Scholar
  31. Korc, M., Ackerman, M.S. and “Roeske, W.R., 1987, A cholinergic antagonist identifies a subclass of muscarinic receptors in isolated rat pancreatic acini. J. Pharmacol. Exp. Ther. 240:118–122.PubMedGoogle Scholar
  32. Laemmli, U.K., 1977, Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 227:680–685.CrossRefGoogle Scholar
  33. 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.PubMedCrossRefGoogle Scholar
  34. 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.PubMedGoogle Scholar
  35. Malhotra, R.K., Wakade, T.D. and Wakade, A.R., 1988, Vasoactive intestinal polypeptide and muscarine mobilize intracellular Ca2+ through breakdown of phosphoinositides to induce catecholamine secretion. J. Biol. Chem. 263:2123–2126.PubMedGoogle Scholar
  36. Mei, L., Lai, J., Roeske, W.R., Fraser, C.M., Venter, J.C. and Yamamura, H.I., 1989a, Pharmacological characterization of the M1 muscarinic receptors expressed in murine fibroblast B82 cells. J. Pharmacol. Exp. Ther. 248:661–670.PubMedGoogle Scholar
  37. Mei, L., Lai, J., Yamamura, H.I. and Roeske, W.R., 1989b, The relationship between agonist states of the M1 muscarinic receptor and the hydrolysis of inositol lipids in transfected murine fibroblast cells (B82) expressing different receptor densities. J. Pharmacol. Exp. Ther. 251:90–97.PubMedGoogle Scholar
  38. Merritt, J.E. and Rink, T.T77 1987, Regulation of cytosolic free calcium in fura-2-loaded rat parotid acinar cells. J. Biol. Chem. 262:17362–17369.PubMedGoogle Scholar
  39. Minta, A., Kao, J.P. and Tsien, R.Y., 1989, Fluorescent indicators for cytosolic calcium based on rhodamine and fluorescein chromophores. J. Biol. Chem. 264:8171–8178.PubMedGoogle Scholar
  40. 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.PubMedCrossRefGoogle Scholar
  41. Peralta, E.G., Ashkenazi, A., Winslow, J.W., Smith, D.H., Ramachandran, J. and Capon, D.J., 1987, Distinct primary structures, ligand-binding properties and tissue specific expression of four human muscarinic acetylcholine receptors. EMB0 J. 6:3923–3929.Google Scholar
  42. Peralta, E.G., Ashkenazi, A., Winslow, J.W., Ramachandran, J. and Capon, D.J., 1988, Differential regulation of PI hydrolysis and adenylyl cyclase by muscarinic receptor subtypes. Nature 334:434–437.PubMedCrossRefGoogle Scholar
  43. 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.PubMedCrossRefGoogle Scholar
  44. Putney, J.W., Jr., 1986, A model for receptor-regulated calcium entry. Cell Calcium 7:1–12.PubMedCrossRefGoogle Scholar
  45. Sanchez-Andres, J.V., Ripoll, C. and Soria, B., 1988, Evidence that muscarinic potentiation of insulin release is initiated by an early transient calcium entry. FEBS lett. 231:143–147.PubMedCrossRefGoogle Scholar
  46. Spat, A., Bradford, P.G., McKinney, J.S., Rubin, R.P. and Putney, J.W., Jr., 1986, A saturable receptor for [32P]-inositol-l,4,5-trisphos-phate in hepatocytes and neutrophils. Nature 319:514–516.PubMedCrossRefGoogle Scholar
  47. Tallarida, R.J. and Murray, R.B., 1987, Manual of PFTarmacologic Calculations with Computer Programs, 2nd ed., pp. 53–56, Spring-Verlag, N.Y.Google Scholar
  48. Tsien, R.Y., Poggan, T. and Rink, T.J., 1982, Calcium homeostasis in intact lymphocytes: cytoplasmic free calcium monitored with a new, intracellularly trapped fluorescent indicator. J. Cell Biol. 94:325–334.PubMedCrossRefGoogle Scholar
  49. Venter, J.C., Eddy, B., Hall, L.M. and Fraser, C.M., 1984, Monoclonal antibodies detect the conservation of muscarinic cholinergic receptor structure from Drosophila to human brain and detect possible structural homology with α1-adrenergic receptors. Proc. Natl. Acad. Sci. 81:272–276.PubMedCrossRefGoogle Scholar
  50. Wang, J.X., Mei, L., Yamamura, H.I. and Roeske, W.R., 1987, Solubilization with digitonin alters the kinetics of pirenzepine binding to muscarinic receptors from rat forebrain and heart. J. Pharm. Exp. Ther. 242:981–990.Google Scholar
  51. Watson, M., Roeske, W.R. and Yamamura, H.I., 1986, [3H]Pirenzepine and (-)-[3H]quinuclidinyl benzilate binding to rat cerebral cortical and cardiac muscarinic cholinergic sites. II. Characterization and regulation of antagonist binding to putative muscarinic subtypes. J. Pharmacol. Exp. Ther. 237:419–427.PubMedGoogle Scholar
  52. Wolf, B.A., Florholmen, J., Turk, J. and McDaniel, W.L., 1988, Studies of the Ca2+ requirements for glucose-and carbachol-induced augmentation of inositol trisphosphate and inositol tetrakisphosphate accumulation in digitonin-permeabilized islets. J. Biol. Chem. 263:3565–3575.PubMedGoogle Scholar

Copyright information

© Plenum Press, New York 1991

Authors and Affiliations

  • Josephine Lai
    • 1
  • Thomas L. Smith
    • 1
    • 6
  • Lin Mei
    • 1
  • Masaaki Ikeda
    • 1
  • Yutaka Fujiwara
    • 1
  • Jorge Gomez
    • 1
    • 5
  • Marilyn Halonen
    • 1
    • 5
  • William R. Roeske
    • 1
    • 3
  • Henry I. Yamamura
    • 1
    • 2
    • 4
  1. 1.Department of PharmacologyUniversity of ArizonaTucsonUSA
  2. 2.Department of PsychiatryUniversity of ArizonaTucsonUSA
  3. 3.Department of Internal MedicineUniversity of ArizonaTucsonUSA
  4. 4.Department of BiochemistryUniversity of ArizonaTucsonUSA
  5. 5.Department of ImmunologyUniversity of ArizonaTucsonUSA
  6. 6.Research ServiceVeterans Administration Medical CenterTucsonUSA

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