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Muscarinic Receptors: Molecular Biology and Neuropsychopharmacology

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Treatment of Dementias

Part of the book series: Advances in Behavioral Biology ((ABBI,volume 40))

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Abstract

Muscarinic and nicotinic are the names given to the two major classes of acetylcholine receptors. These receptors play major roles in the function of the body. In brain, evidence suggests a role for muscarinic receptors in memory function. Therefore, these receptors have been a focus of interest for the therapeutics of Alzheimer’s disease.

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References

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

    CAS  Google Scholar 

  2. M. Raiteri, R. Leardi, and M. Marchi, Heterogeneity of presynaptic muscarinic receptors regulating neurotransmitter release in the rat brain, J. Pharmacol. Exp. Ther. 228: 209 (1984).

    PubMed  CAS  Google Scholar 

  3. A. Akaike, M. Sasa, and S. Takaori, Muscarinic inhibition as a dominant role in cholinergic regulation of transmission in the caudate nucleus, J. Pharmacol. Exp. Ther. 246: 1129 (1988).

    PubMed  CAS  Google Scholar 

  4. E.S. Vizi, O. Kobayashi, A. Torocsik, M. Kinjo, H. Nagashima, N. Manabe, P.L. Goldiner, P.E. Potter, and F.F. Foldes, Heterogeneity of presynaptic muscarinic receptors involved in modulation of transmitter release. Neuroscience 31: 259 (1989).

    Article  PubMed  CAS  Google Scholar 

  5. M. Raiteri, M. Marchi, P. Paudice, and A. Pittaluga, Muscarinic receptors mediating inhibition of Îł-aminobutyric acid release in rat corpus striatum and their pharmacological characterization, J. Pharmacol. Exp. Ther. 254: 496 (1990).

    PubMed  CAS  Google Scholar 

  6. J.K. Wamsley, M.A. Zarbin, and M.J. Kuhar, Distribution of muscarinic cholinergic high and low affinity agonist binding sites:a light microscopic autoradiographic study, Brain Res. Bull. 12: 233 (1984).

    CAS  Google Scholar 

  7. R. Cortes, A. Probst, H.J. Tobler, and J.M. Palacios, Muscarinic cholinergic receptor subtypes in the human brain. II. quantitative autoradiographic studies, Brain Res. 362: 239 (1986).

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  10. E.G. Peralta, J.W. Sinslow, G.L. Peterson, D.H. Smith, A. Ashkenazi, J. Ramachandran, M.I. Schimerlik, and D.J. Capon, Primary structure and biochemical properties of an M2 muscarinic receptor, Science 236: 600 (1987).

    Article  PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  12. T.I. Bonner, A.C. Young, M.R. Brann, and N.J. Buckley, Cloning and expression of the human and rat M5 muscarinic acetylcholine receptor genes, Neuron 1: 403 (1988).

    Article  PubMed  CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  14. P. Davies and B.L. Woloszin, Recent advances in the neurochemistry of Alzheimer’s Disease, J. Clin. Psychiatry 48: 23 (1987).

    PubMed  Google Scholar 

  15. M. McKinney and E. Richelson, The coupling of the neuronal muscarinic receptor to responses, Ann. Rev. Pharmacol. Toxicol. 24: 121 (1984).

    Article  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  17. E.J. Neer and D.E. Clapham, Roles of G protein subunits in transmembrane signalling, Nature 333: 129 (1988).

    Article  PubMed  CAS  Google Scholar 

  18. K. Tanaka, M. Masu, and S. Nakanishi, Structure and functional expression of the cloned rat neurotensin receptor, Neuron 4: 847 (1990).

    Article  PubMed  CAS  Google Scholar 

  19. I. Gantz, M. Schaffer, J. Delvalle, C. Logsdon, V. Campbell, M. Uhler, and T. Yamada, Molecular cloning of a gene encoding the histamine H2 receptor, Proc. Natl. Acad. Sci. USA 88: 429 (1991).

    Article  PubMed  CAS  Google Scholar 

  20. H.-Y. Wang, L. Lipfer, C.C. Malbon, and S. Bahouth, Site directed anti-peptide antibodies define the topography of the β-adrenergic receptor, J. Biol. Chem. 264: 14424 (1989).

    PubMed  CAS  Google Scholar 

  21. R.K. Goyal and S. Rattan, Neurohumoral, hormonal and drug receptors for the lower esophageal sphincter, Gastroenterology 74: 598 (1978).

    PubMed  CAS  Google Scholar 

  22. V.W. Eberlein, G. Schmidt, A. Reuter, and E. Kutter, Anti-ulcer agent pirenzepine (L-S 519) — a tricyclic compound with particular physico-chemical properties, Arzneim-Forsch/Drug Res. 27: 356 (1977).

    CAS  Google Scholar 

  23. R. Hammer, C.P. Berrie, NJ.M. Birdsall, A.S.V. Burgen, and E.C. Hulme, Pirenzepine distinguishes between different subclasses of muscarinic receptors, Nature 283: 90 (1980).

    Article  PubMed  CAS  Google Scholar 

  24. M. Waelbroeck, M. Tastenoy, J. Camus, and J. Christophe, Binding of selective antagonists to four muscarinic receptors (Ml to M4) in rat forebrain, Mol. Pharmacol. 38: 267 (1990).

    CAS  Google Scholar 

  25. N. Birdsall, N. Buckley, H. Doods, K. Fukuda, A. Giachetti, R. Hammer, H. Kilbinger, G. Lambrecht, E. Mutschler, N. Nathanson, A. North, and R. Schwarz, Nomenclature for muscarinic receptor subtypes recommended by symposium, Trends Pharmacol. Sci. [Suppl] Dec.:Vii (1989).

    Google Scholar 

  26. F. Dorje, J. Wess, G. Lambrecht, R. Tacke, E. Mutschler, and M.R. Brann, Antagonist binding profiles of five cloned human muscarinic receptor subtypes, J. Pharmacol. Exp. Ther. 256: 727 (1990).

    Google Scholar 

  27. S.-C. Lin, K. Olson, H. Okazaki, and E. Richelson, Studies on muscarinic binding sites in human brain identified with [3H]pirenzepine, J. Neurochem. 46: 274 (1986).

    Article  PubMed  CAS  Google Scholar 

  28. S.J. Wall, R.P. Yasuda, F. Hory, S. Flagg, B.M. Martin, E.I. Ginns, and B.B. Wolfe, Production of antisera selective for M1-muscarinic receptors using fusion proteins — distribution of M1-receptors in rat brain, Mol. Pharmacol. 39: 643 (1991).

    CAS  Google Scholar 

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

    PubMed  CAS  Google Scholar 

  30. M.T. Vilaro, J.M. Palacios, and G. Mengod, Localization of M5 muscarinic receptor mRNA in rat brain examined by in situ hybridization histochemistry, Neurosci. Lett. 114: 154 (1990).

    CAS  Google Scholar 

  31. M.J. Blake, N.M. Appel, J.A. Joseph, C.A. Stagg, M. Anson, E.B. De Souza, and G.S. Roth, Muscarinic acetylcholine receptor subtype mRNA expression and ligand binding in the aged rat forebrain, Neurobiol. Aging 12: 193 (1991).

    CAS  Google Scholar 

  32. M.J. Berride, Receptors and calcium signalling, Trends Pharmacol. Sci. (November): 419 (1980).

    Google Scholar 

  33. S. Lazareno, D.A. Kendall, and S.R. Nahorski, Pirenzepine indicates heterogeneity of muscarinic receptors linked to cerebral inositol phospholipid metabolism, Neuropharmacology 24: 593 (1985).

    Article  PubMed  CAS  Google Scholar 

  34. C. Forray and E.E. El-Fakahany, On the involvement of multiple muscarinic receptor subtypes in the activation of phosphoinositide metabolism in rat cerebral cortex, Mol. Pharmacol. 37: 893 (1990).

    CAS  Google Scholar 

  35. M. Mckinney, D.J. Anderson, L. Vellarountree, T. Connolly, and J.H. Miller, Pharmacological profiles for rat cortical Ml and M2 muscarinic receptors using selective antagonists — comparison with N1E-115 muscarinic receptors, J. Pharmacol. Exp. Ther. 257: 1121 (1991).

    PubMed  CAS  Google Scholar 

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

    Article  PubMed  CAS  Google Scholar 

  37. R. Stein, R. Pinkas-Kramarski, and M. Sokolovsky, Cloned Ml muscarinic receptors mediate both adenylate cyclase inhibition and phosphoinositide turnover. EMBO J. 7: 3031 (1988).

    PubMed  CAS  Google Scholar 

  38. R.T. Bartus, R.L. Dean III, B. Beer, A.S. Lippa, The cholinergic hypothesis of geriatric memory dysfunction, Science 217: 408 (1982).

    Article  PubMed  CAS  Google Scholar 

  39. N. Sitaram, Cholinergic hypothesis of human memory:review of basic and clinical studies, Drug Develop. Res. 4: 481 (1984).

    CAS  Google Scholar 

  40. W.S.J. Messer, G.J. Thomas, W. Hoss, Selectivity of pirenzepine in the central nervous system. II. Differential effects of pirenzepine and scopolamine on performance of a representational memory task, Brain Res. 407: 37 (1987).

    Article  PubMed  CAS  Google Scholar 

  41. T.L. Yaksh, R. Dirksen, G.J. Harty, Antinociceptive effects of intrathecally injected cholinomimetic drugs in the rat and cat, Eur. J. Pharmacol. 117: 81 (1985).

    Article  PubMed  CAS  Google Scholar 

  42. R.L. Kohl, M.R. Lewis, Mechanisms underlying the antimotion sickness effects of psychostimulants, Aviat. Space Environ. Med. 58: 1215 (1987).

    CAS  Google Scholar 

  43. J. Velazquez-Moctezuma, J.C. Gillin, P.J. Shiromani, Effect of specific Ml, M2 muscarinic receptor agonists on REM sleep generation, Brain Research 503: 128 (1989).

    Article  PubMed  CAS  Google Scholar 

  44. V. Coiro, R. Volpi, P. Muzzetto, A. Caiazza, R. Petrolini, Cerri, R. Ruberti, and P. Chiodera, Cholinergic-muscarinic receptors participate in growth hormone secretion induced by lysine-8-vasopressin in man, Horm. Metabol. Res. 17: 316 (1985).

    Article  CAS  Google Scholar 

  45. P. Carmeliet, C. Denef, Immunocytochemical and pharmacological evidence for an intrinsic cholinomimetic system modulating prolactin and growth hormone release in rat pituitary, Endocrinology 123: 1128 (1988).

    Article  PubMed  CAS  Google Scholar 

  46. D.S. Janowsky, M.K. El-Yousef, J.M. Davis, H.J. Sekerke, A cholinergic-adrenergic hypothesis of mania and depression, Lancet 1: 632 (1972).

    Article  Google Scholar 

  47. J. Sitaram, J.I. Nurnberger Jr., E.S. Gershon, J.C. Gillin, Cholinergic regulation of mood and REM sleep:potential model and marker of vulnerability to effective disorder, Am. J. Psychiatry 139: 571 (1982).

    PubMed  CAS  Google Scholar 

  48. DJ. Safer and R.P. Allen, The central effects of scopolamine in man, Biol. Psychiatry 3: 347 (1971).

    CAS  Google Scholar 

  49. D.A. Drachman and J. Leavitt, Human memory and the cholinergic system. A relationship to aging?, Arch. Neurol. 30: 113 (1974).

    CAS  Google Scholar 

  50. P. Davies and A.J.F. Maloney, Selective loss of central cholinergic neurons in Alzheimer’s disease, Lancet 11: 1403 (1976).

    Article  Google Scholar 

  51. E.K. Perry, R.H. Perry, G. Blessed, and B.E. Tomlinson, Necropsy evidence of central cholinergic deficits in senile dementia, Lancet 1: 189 (1977).

    Article  PubMed  CAS  Google Scholar 

  52. H.C. Fibiger, Cholinergic mechanisms in learning, memory and dementia — a review of recent evidence, Trends Neurosci. 14: 220 (1991).

    Article  PubMed  CAS  Google Scholar 

  53. C. Bolden, B. Cusack, and E. Richelson, Clozapine is a potent and selective muscarinic antagonist at the five cloned human muscarinic acetylcholine receptors expressed in CHO-K1 cells, Eur. J. Pharmacol. 192: 205 (1991).

    Article  PubMed  CAS  Google Scholar 

  54. C.P. Bolden, B. Cusack, and E. Richelson, Clozapine is a potent and selective antagonist at the five cloned human muscarinic cholinergic receptors, FASEB J. 5: A487 (1991).

    Google Scholar 

  55. P. Davies and A.H. Verth, Regional distribution of muscarinic acetylcholine receptor in normal and Alzheimer’s-type dementia brains, Brain Res. 138: 385 (1978).

    Article  Google Scholar 

  56. B.L. Holman, R.E. Gibson, T.C. Hill, W.C. Eckelman, M. Albert, and R.C. Reba, Muscarinic acetylcholine receptors in Alzheimer’s disease, JAMA 254: 3063 (1985).

    Article  PubMed  CAS  Google Scholar 

  57. D.C. Mash, D.D. Flynn, and L.T. Potter, Loss of M2 muscarine receptors in the cerebral cortex in Alzheimer’s disease and experimental cholinergic denervation, Science 228: 1115 (1985).

    Article  PubMed  CAS  Google Scholar 

  58. J.O. Rinne, K. Laakso, P. Lonnberg, P. Molsa, L. Paljarvi, J.K. Rinne, E. Sako, and U.K. Rinne, Brain muscarinic receptors in senile dementia, Brain Res. 336: 19 (1985).

    Article  PubMed  CAS  Google Scholar 

  59. A. Nordberg, I. Alafuzoff, and B. Winblad, Muscarinic receptor subtypes in hippocampus in Alzheimer’s disease and mixed dementia type, Neurosci. Lett. 70: 160 (1986).

    CAS  Google Scholar 

  60. S. Shimohama, T. Taniguchi, M. Fujiwara, and M. Kameyama, Changes in nicotinic and muscarinic cholinergic receptors in Alzheimer-type dementia, J. Neurochem. 46: 288 (1986).

    Article  PubMed  CAS  Google Scholar 

  61. K.J. Reinikainen, P.J. Riekkinen, T. Halonen, and M. Laakso, Decreased muscarinic receptor binding in cerebral cortex and hippocampus in Alzheimer’s disease, Life Sci. 41: 453 (1987).

    Article  PubMed  CAS  Google Scholar 

  62. K.J. Kellar, P.J. Whitehouse, and A.M.E.A. Martino-Barrows, Muscarinic and nicotinic cholinergic binding sites in Alzheimer’s disease cerebral cortex, Brain Res. 436: 62 (1987).

    Article  PubMed  CAS  Google Scholar 

  63. E. Danielsson, S.-A. Eckernas, A. Westlind-Danielsson, O. Nordstrom, T. Bartfai, C.-G. Gottfries, and A. Wallin, VIP-sensitive adenylate cyclase, guanylate cyclase, muscarinic receptors, choline acetyltransferase and acetylcholinesterase, in brain tissue afflicted by Alzheimer’s disease/senile dementia of the Alzheimer type, Neurobiol. Aging 9: 153 (1988).

    CAS  Google Scholar 

  64. A. Probst, R. Cortes, J. Ulrich, and J.M. Palacios, Differential modification of muscarinic cholinergic receptors in the hippocampus of the patients with Alzheimer’s disease:an autoradiographic study. Brain Res. 450: 190 (1988).

    Article  PubMed  CAS  Google Scholar 

  65. K.W. Lange, F.R. Wells, M.N. Rossor, P. Jenner, and C.D. Marsden, Brain muscarinic receptors in Alzheimer’s and Parkinson’s diseases, Lancet November 25: 1279 (1989).

    Article  Google Scholar 

  66. J.O. Rinne, P. Lonnberg, P. Marjamaki, and U.K. Rinne, Brain muscarinic receptor subtypes are differently affected in Alzheimer’s disease and Parkinson’s disease, Brain Res. 483: 402 (1989).

    Article  PubMed  CAS  Google Scholar 

  67. R. Quirion, I. Aubert, P.A. Lapchak, R.P. Schaum, S. Teolis, S. Gauthier, and D.M. Araujo, Muscarinic receptor subtypes in human neurodegenerative disorder:focus on Alzheimer’s disease, Subtypes of Muscarinic Receptors, Trends, Pharmacol. Sci. IV, Suppl.: 80 (1990).

    Google Scholar 

  68. J.B. Penney, W.F. Maragos, J.T. Greenamyre, D.L. Debowey, Z. Hollingsworth, and A.B. Young, Excitatory amino acids binding sites in the hippocampal region of Alzheimer’s disease and other dementias, J. Neurol., Neurosurg., Psychiat. 53: 314 (1990).

    Article  CAS  Google Scholar 

  69. E.K. Perry, C.J. Smith, J.A. Court, and R.H. Perry, Cholinergic nicotinic and muscarinic receptors in dementia of Alzheimer, Parkinson and Lewy body types, J. Neural Transm. [P-D Sect] 2: 149 (1990).

    Article  CAS  Google Scholar 

  70. T. Sakurada, I. Alufuzoff, B. Winblad, and A. Nordberg, Substance P-like immunoreactivity, choline acetyltransferase activity and cholinergic muscarinic receptors in Alzheimer’s disease and multi-infarct dementia, Brain Research 521: 329 (1990).

    Article  PubMed  CAS  Google Scholar 

  71. B.A. Vogt, P.B. Crino, and L. Volicer, Laminar alterations in γ-aminobutyric acidA, muscarinic, and β-adrenoceptors and neuron degeneration in cingulate cortex in Alzheimer’s disease, J. Neurochem. 57: 282 (1991).

    Article  PubMed  CAS  Google Scholar 

  72. S. Shimohama, T. Taniguchi, M. Fujiwara, and M. Kameyama, Changes in nicotinic and muscarinic cholinergic receptors in Alzheimer-type dementia, J. Neurochem. 46: 288 (1986).

    Article  PubMed  CAS  Google Scholar 

  73. K.J. Kellar, P.J. Whitehouse, A.M. Martino-Barrows, K. Marcus, and D.L. Price, Muscarinic and nicotinic cholinergic binding sites in Alzheimer’s disease cerebral cortex, Brain Res. 436: 62 (1987).

    Article  PubMed  CAS  Google Scholar 

  74. P.J. Whitehouse, A.M. Maitino, K.A. Marcus, R.M. Zweig, H.S. Singer, D.L. Price, and K.J. Kellar, Reductions in acetylcholine and nicotine binding in several degenerative disease, Arch. Neurol. 45: 722 (1988).

    CAS  Google Scholar 

  75. D.M. Araujo, P.A. Lapchak, Y. Robitaille, S. Gauthier, and R. Quirion, Differential alteration of various cholinergic markers in cortical subcortical regions of human brain in Alzheimer’s disease, J. Neurochem. 50: 1914 (1988).

    Article  PubMed  CAS  Google Scholar 

  76. E.D. London, M.J. Ball, and S.B. Waller, Nicotinic binding sites in cerebral cortex and hippocampus in Alzheimer’s dementia, Neurochem. Res. 14: 745 (1989).

    CAS  Google Scholar 

  77. K. Sugaya, E. Giacobini, and V.A. Chiappinelli, Nicotinic acetylcholine receptor subtypes in human frontal cortex:changes in Alzheimer’s disease, J. Neurosci. Res. 27: 349 (1990).

    Article  PubMed  CAS  Google Scholar 

  78. H. Schroder, E. Giacobini, R.G. Struble, K. Zilles, and A. Maelicke, Nicotinic cholinoceptive neurons of the frontal cortex are reduced in Alzheimer’s disease, Neurobiol. Aging 12: 259 (1991).

    CAS  Google Scholar 

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Richelson, E. (1992). Muscarinic Receptors: Molecular Biology and Neuropsychopharmacology. In: Meyer, E.M., Simpkins, J.W., Yamamoto, J., Crews, F.T. (eds) Treatment of Dementias. Advances in Behavioral Biology, vol 40. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-3432-7_1

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