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 ch aracterize the receptors which mediate carbachol-evoked contractions o f intertaenial circular and taenial longitudinal muscle in human isola ted colon. The effects of these antagonists were studied upon colon co ntractions induced by cumulatively added carbachol which had mean EC(5 0) values of 11.7 +/- 2.3 mu M (n = 8) and 12.6 +/- 2.3 mu M (n = 8) r espectively upon circular and longitudinal smooth muscle, 2 All antago nists displaced concentration-response curves to carbachol to the righ t in a parallel manner. The maximum concentration of each antagonist a dded (30 nM-10 mu M) did not significantly suppress the maximum respon se. 3 In circular muscle, the M(3) muscarinic receptor antagonists, 4- diphenylacetoxy-N-methylpiperidine methiodide (4-DAMP), hexahydrosilad iphenidol (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, a nd 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, himbac ine 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 respectivel y. Atropine yielded a pA(2) value of 8.60 +/- 0.08. 5 The pharmacologi cal profile of antagonist affinities at the muscarinic receptor popula tion responding to muscarinic agonist-evoked contraction is similar to that widely accepted as characterizing the activation of an M(3) musc arinic receptor subtype, although pA(2) values of some antagonists are lower than that seen in other investigations.