Depolarisation of guinea-pig visceral smooth muscle causes hydrolysis of inositol phospholipids.

Increasing concentrations of KCl caused a progressive stimulation of contractile activity in guinea-pig jejunal longitudinal smooth muscle strips, accompanied by increased production of [3H]inositol phosphates in smooth muscle fragments pre-labelled with myo-[3H]inositol. The concentration-response curve for contractility lay to the left of that for [3H]inositol phosphate production. Both responses showed a dependency on the presence of Ca2+ in the incubation medium. K+-induced contractility was abolished by D600 or by Mn2+, whereas stimulated [3H]inositol phosphate formation persisted in the presence of these Ca2+ channel blockers. The simultaneous addition of high KCl concentrations together with a maximal concentration of neurotransmitter (carbamylcholine of substance P) produced additive stimulation of [3H]inositol phosphate production. Enhanced production of [3H]inositol phosphates was also observed under a variety of conditions known to cause smooth muscle depolarisation, including omission from the incubation medium of Na+ or K+, and in response to ouabain or veratridine. The results suggest that inositol lipid hydrolysis in visceral longitudinal smooth muscle may be triggered by depolarisation, an event which causes the entry of Ca2+ into the cell but which is not generally believed to cause the release of stored Ca2+ within the cell. However, calcium entry seems not to be essential for the effect on inositol lipid hydrolysis.