ON THE ACTION OF PROSTAGLANDIN E1AND PROSTAGLANDINS FROM BRAIN ON THE ISOLATED RAT STOMACH

Abstract

Prostaglandins are a group of structurally related dihydroxyketo- and trihydroxy-C20 unsaturated carboxylic acids which cause contraction of intestinal smooth muscle at concentrations down to 1 x 10-10 g/ml. Crystalline prostaglandin Ey and a purified preparation of ox brain prostaglandlns (mainly F2[alpha]) initiated contraction of the isolated rat stomach fundus preparation by a direct action on the muscle which was strongly antagonized by adrenalin [eplnephrine] and noradrenalln [norepinephrine]. Drugs that inhibited sympathetic fibers or receptors potentiated the action of prostaglandins, whereas drugs that stimulated sympathetic receptors were inhibitory. Prostaglandin action was greatly diminished by lowering the temperature from 37[degree] C to 24[degree] C. The presence of oxygen was absolutely necessary for initiation of prostaglandin contraction but not for acetylcholine contraction. Prostaglandlns were taken up by the tissue or produced a persistent change when added under anoxic conditions, but were unable to act unless oxygen was present. Metabolic inhibitors such as cyanide, azide, and carbon monoxide reverslbly inhibited prostaglandin action to a greater extent than that of acetylcholine. A tonic rebound contraction occurred after removal of these inhibitors. Ascorbic acid and reduced (but not oxidized) glutathione reversibly enhanced prostaglandin action. Increased external potassium progressively increased the sensitivity of the muscle to prostaglandlns. A hypothesis is proposed in which prostaglandins in association with an oxygen-requiring metabolic reaction initiate contraction by the release of bound calcium or the facilitation of calcium influx.