Relaxant effects of sulfonylureas on induced contractions of rat uterine smooth muscle: role of intracellular calcium.

We have investigated the action of tolbutamide and glibenclamide in a Ca-dependent process: the contractile activity of smooth muscle (uterus). The results obtained show that sulfonylureas are capable of relaxing contractions of rat uterus induced by various agents: oxytocin, acetylcholine and KCl in a medium with Ca2+. The capacity of sulfonylureas to also relax oxytocin-induced Ca-free contraction indicates the possibility that the action of these drugs could be due, above all, to a decrease in the intracellular free calcium level. Since maintained contraction induced by oxytocin in a Ca-free solution could be repeated after making a relaxation dose-response curve to sulfonylurea, the most likely mechanism of sulfonylurea-induced uterine relaxation is not an increase in the efflux of Ca but an increase in the Ca-uptake by intracellular organelles.