CHARACTERIZATION OF MUSCARINIC RECEPTORS MEDIATING CONTRACTIONS OF CIRCULAR AND LONGITUDINAL MUSCLE OF HUMAN ISOLATED COLON

1 The effects of seven muscarinic receptor antagonists were used to characterize the receptors which mediate carbachol-evoked contractions of intertaenial circular and taenial longitudinal muscle in human isolated colon. The effects of these antagonists were studied upon colon contractions induced by cumulatively added carbachol which had mean EC(50) values of 11.7 +/- 2.3 mu M (n = 8) and 12.6 +/- 2.3 mu M (n = 8) respectively upon circular and longitudinal smooth muscle, 2 All antagonists displaced concentration-response curves to carbachol to the right in a parallel manner. The maximum concentration of each antagonist added (30 nM-10 mu M) did not significantly suppress the maximum response. 3 In circular muscle, the M(3) muscarinic receptor antagonists, 4-diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP), hexahydrosiladiphenidol (HHSiD) and para-fluoro-hexahydrosiladiphenidol (p-F-HHSiD) inhibited responses with pA(2) values of 9.41 +/- 0.23, 7.17 +/- 0.07, 6.94 +/- 0.18, respectively. The M(2) muscarinic receptor antagonist, AF-DX 116, the M(2)/M(4) muscarinic receptor antagonist, himbacine, and the M(1) muscarinic receptor antagonist, pirenzepine, yielded pA(2) values of 7.36 +/- 0.43, 7.47 +/- 0.14 and 7.23 +/- 0.48 respectively. The non-selective antagonist, atropine, had a pA(2) of 8.72 +/- 0.28. 4 In longitudinal muscle 4-DAMP, HHSiD, p-F-HHSiD, AF-DX 116, himbacine and pirenzepine gave pA(2) values of 9.09 +/- 0.16, 7.45 +/- 0.43, 7.44 +/- 0.21, 6.44 +/- 0.1, 7.54 +/- 0.40, 6.87 +/- 0.38 respectively. Atropine yielded a pA(2) value of 8.60 +/- 0.08. 5 The pharmacological profile of antagonist affinities at the muscarinic receptor population responding to muscarinic agonist-evoked contraction is similar to that widely accepted as characterizing the activation of an M(3) muscarinic receptor subtype, although pA(2) values of some antagonists are lower than that seen in other investigations.