The Molecular Properties of the M1 Muscarinic Receptor and its Regulation of Cytosolic Calcium in a Eukaryotic Gene Expression System
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.
KeywordsHydrolysis Electrophoresis Polypeptide Catecholamine Ampicillin
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