The effect of cisapride on smooth muscle cells of guinea-pig taenia caeci.

Cisapride (5 X 10(-7) M) caused depolarization, enhancement of spike activity, increase in muscle tone and potentiation of the contraction evoked by transmural stimulation of taenia caecum of the guinea-pig at 35 degrees C. At higher cisapride concentrations (2.5 X 10(-6) M) the potentiation of the evoked contraction was less pronounced or was even reversed into inhibition. Muscle tone was also enhanced by cisapride after relaxation of the smooth muscle cells by isobutylmethylxanthine (4 X 10(-5) M), a phosphodiesterase inhibitor. This effect of cisapride on muscle tone was smaller in the presence of atropine (10(-6) M), prazosin (10(-6) M) and propranolol (10(-6) M) and was also decreased in the presence of tetrodotoxin (3 X 10(-7) M). With these receptor blocking agents cisapride (5 X 10(-7) M) also depolarized smooth muscle cells and increased spike activity. The amplitude of the inhibitory junction potential represented by hyperpolarization was also enhanced and was followed by a more pronounced rebound activity. The depolarization induced by cisapride persisted in low sodium-low chloride and calcium-free solution, respectively. The cisapride depolarization was completely inhibited in the presence of orthovanadate (1 mM). It is concluded that cisapride inhibits calcium extrusion by a direct action on the smooth muscle cells of taenia caecum, leading to depolarization and enhancement of electrical and mechanical activity.