Mechanism of chloroquine-induced inhibition of smooth muscle contraction.

The study was designed to characterize the mechanism of chloroquine-induced depression of contractility in isolated rat ileal smooth muscle. Chloroquine (10(-7)-10(-4) M) depressed both spontaneous as well as 10(-7) M acetylcholine-induced contractions dose-dependently. The decline in contractile responses to maximal dose of Ach (10(-6) M) in Ca-free medium was significantly increased by treatment with chloroquine. Restoration of Ca++ to Ach-stimulated "Ca-depleted" tissues produced contractions due to Ca++ influx; these contractions were prevented by chloroquine, dose-dependently. Using "Ca-loading" and "Ca-washing" procedures 10(-6) M Ach was observed to mobilize Ca++ from a "membrane-bound" pool, perhaps containing residual Ca++ of extracellular origin. Chloroquine significantly inhibited the rate of filling of such "membrane-bound" pool. The results show that chloroquine-induced depression of mechanical activity of the rat ileal smooth muscle is associated with diminished Ca++ influx, as well as impaired mobilization of Ca++ from an Ach-sensitive "membrane-bound" pool.