The mechanism of action of ionophore A 23187 on guinea pig intestinal smooth muscle

Abstract

The cation ionophore A 23187 [2-[(3.beta.,9.alpha.,11.beta.-trimethyl)-8-[2-(pyrrole carboxymethyl)-1,7-dioxaspiro[6.6] undecyl-2.beta.-methyl]-5-methyl aminobenzoxazole-4-carboxylic acid]] behaves similarly to the potent muscarinic agonist, cis-2-methyl-4-dimethylaminomethyl-1,3-dioxolane methiodide (CD) in guinea pig ileal longitudinal smooth muscle generating contractile responses that are gradedly sensitive to the concentrations of Ca2+ext and Na+ext. A 23187 and CD responses are insensitive to tetrodotoxin and A 23187 responses are insensitive to atropine. The responses to CD, A 23187, and veratridine are all similarly sensitive to the Ca antagonists D 600 [.alpha.-isopropyl .alpha.-[(N-methyl-N-homoveratryl-.alpha.-aminopropyl)]-3,4,5-trimethoxyphenylacetonitrile] and BAY-1040 [Nifedipine]. D 600 failed to antagonize the ability of A 23187 to transport Ca2+ in a toluene-butanol:water 2-phase system. It is suggested that in guinea pig ileal smooth muscle A 23187 does not translocate Ca2+ext exclusively but serves also to activate Ca2+ channels perhaps by an initial depolarizing Na+ entry.