Interaction of selective compounds with muscarinic receptors at dispersed intestinal smooth muscle cells

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Abstract
1 The characterization of muscarinic receptors on single cells of the guinea-pig ileum longitudinal smooth muscle, devoid of neuronal elements, was functionally studied by estimating the affinities of muscarinic antagonists on acetylcholine-induced contractions. 2 Atropine (5 × 10−11 to 5 × 10−6 m), 4-diphenylacetoxy-N-methyl-piperidine methiodide (4-DAMP, 5 × 10−8 to 5 × 10−6 m), cyclohexyl(4-fluoro-phenyl) (3-piperidinopropyl) silanol (pFHHSiD, 5 × 10−7 to 5 × 10−5 m) as well as pirenzepine (5 × 10−7 to 5 × 10−5 m) competitively antagonized the acetylcholine-dependent contractions with different affinities (atropine > 4-DAMP > pFHHSiD > pirenzepine). 3 Methoctramine (5 × 10−7 to 5 × 10−5 m), and AF-DX 116 (5 × 10−6 and 5 × 10−5 m) also showed antagonist properties but these deviated from simple competition. These compounds, which discriminate between M2 and M3 receptors, showed a potency lower than that of pirenzepine, the rank order of potencies being pirenzepine > methoctramine > AF-DX 116. When concentrations of AF-DX 116, methoctramine and pirenzepine were increased an unspecific contractile effect occurred. 4 McN-A-343, a partial agonist on intact guinea-pig longitudinal smooth muscle strips, on this preparation induced a weak contraction (about 7% in comparison to control) that was not reversed by antimuscarinic agents. 5 These data indicate that M3 rather than M2 receptor sites are present on this tissue.