Effect of prostacyclin (PGI2) on the mechanical activity of isolated longitudinal and circular muscle strips of guinea-pig stomach

Abstract

Muscle strips isolated in longitudinal and circular directions from the fundus, corpus and antrum, and from the pyloric sphincter of the guinea-pig stomach were placed in organ baths for recording their spontaneous contractility. Concentrations of the order of 10(-9) to 10(-6) M of prostacyclin (PGI2) were tested and compared with the effect of PGE1, PGE2, PGF2 alpha and acetylcholine. Furthermore, a modification of PGI2 effect was studied in the presence of adrenergic and cholinergic blocking agents, tetrodotoxin, indomethacin and the PG antagonist SC-19220. Like PGE1, PGE2, PGF2 alpha and acetylcholine, PGI2 increased the tone of the longitudinal strips from fundus, corpus and antrum, its effect being less potent than the effects of PGE1 and PGE2 and more potent than the effects of PGF2 alpha and acetylcholine. All the PGs inhibited the phasic contractions of the circular muscle of antrum and pyloric sphincter in a dose-dependent manner. These effects were not significantly changed in the presence of adrenergic and cholinergic blocking agents, nor in the presence of tetrodotoxin, and could therefore be interpreted as being myogenic in nature. Indomethacin exerted effects opposite to those of PGI2. It shifted the log concentration-effect curve for PGI2 to the right suppressing the maximum response of PGI2 by about 50%. SC-19220 reversibly inhibited the spontaneous tone and the excitatory responses of the gastric muscle to PGI2. The concentration-effect curves for PGI2 were shifted to the right in the presence of SC-19220. Analysis of the data gave the pA2 value for PGI2 5.3, the slope of Schild plot being 1.23, which suggests that SC-19220 is a competitive antagonist.