Actions of various muscarinic agonists on membrane potential, potassium efflux, and contraction of longitudinal muscle of guinea-pig intestine.

1 Depolarizations were recorded intracellularly in smooth muscle from the taenia of the guinea-pig caecum in response to the iontophoretic application of acetylcholine, carbachol, oxotremorine-M, methylfurmethide, hexyl trimethylammonium and tetramethylammonium (TMA). 2 No differences between the iontophoretic responses to agonists stable to cholinesterase were detected. 3 The latency and time to peak of acetylcholine-induced depolarizations were less than those to stable agonists, and the response was briefer and less complex in shape. These differences were reduced, or disappeared, upon inhibition of cholinesterase. 4 The rate of loss of 42K and changes in length were measured in superfused strips weighing about 10 mg of separated longitudinal muscle of guinea-pig ileum. 5 Acetylcholine, carbachol, methylfurmethide, butyltrimethylammonium and TMA contracted the muscle and increased the rate of loss of 42K. 6 Contrary to previous reports, no evidence of a selective action of any of these agonists on 42K loss was detected. TMA appeared to be a partial agonist in evoking 42K loss, although it produced a maximum contraction. 7 The maximum 42K efflux produced by acetylcholine was about 40% of the maximum evoked by application of carbachol or methylfurmethide. If cholinesterase was inhibited, the 42K efflux evoked by maximally effective concentrations of acetylcholine was comparable to that evoked by a stable agonist. 8 These results are consistent with the idea that the muscarinic agonists used interact in an essentially similar way with muscarinic receptors to produce their effects on membrane potential, permeability, and tension.