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.
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000502:physiology; D002738:Chloroquine / Q000494:pharmacology*; D066298:In Vitro Techniques; D007537:Isometric Contraction / Q000187:drug effects; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D009130:Muscle, Smooth / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D051381:Rats; D011919:Rats, Inbred Strains
D002738:Chloroquine; D000109:Acetylcholine; D002118:Calcium