Inhibitory effects of dantrolene on contractile responses in gastric smooth muscle of the rat.

Abstract

Effects of dantrolene on contractions evoked by KCl, carbachol (CCh) and caffeine were studied in the circular smooth muscle of rat stomach. Dantrolene (10-100 microM) suppressed contractions evoked by KCl (40 mM) and CCh (1 microM), but not those induced by caffeine (3 mM) in physiological saline. After intracellular Ca stores were depleted by treatment with ryanodine (50 microM) plus caffeine (10 mM), or by repetitive applications of caffeine (10 mM) or CCh (0.1 mM) in the absence of extracellular Ca, combined application of KCl (150 mM) with Ca (2.5 mM) or CCh (1 microM) with Ca (2.5 mM) elicited contractions which were due to Ca influx. Nifedipine (10 microM) almost abolished the contractions induced by KCl, but only partially reduced the contractions induced by CCh. Dantrolene inhibited contractions induced by KCl with various concentrations of Ca (0.3-10 mM), and those induced by CCh with Ca (1-10 mM) in the presence of nifedipine. Dantrolene failed to inhibit the caffeine- and CCh-induced contractions depending on intracellularly stored Ca. In skinned muscle preparations, dantrolene had no effect on the contractions induced by Ca (6.3 x 10(-7M). These results suggest that dantrolene inhibits Ca influx through both nifedipine-sensitive and -resistant pathways of the plasma membrane but does not affect Ca release from intracellular stores and the contractile machinery in the circular smooth muscle of rat stomach.