Antagonistic effect of SC-19220 on the responses of guinea-pig gastric muscles to prostaglandins E1, E2 and F2 alpha.

SC-19220 has been studied for its ability to antagonize the contractions produced by prostaglandins E1, E2 and F2 alpha (PGE1, PGE2, PGF2 alpha) on isolated guinea-pig gastric muscle. At concentrations of 1 X 10(-6) M to 3 X 10(-4) M SC-19220 inhibited reversibly in a dose-dependent manner both the spontaneous tone and the phasic activity. At the same concentrations the compound had no effect on the inhibitory responses of circular muscle strips to PGE1, PGE2 and PGF2 alpha. In contrast, SC-19220 antagonized the excitatory responses of longitudinal muscle strips to PGE1, PGE2 and PGF2 alpha. The concentration-effect curves for PGE1, PGE2 and PGF2 alpha were shifted to the right. Analysis of the data ( Arunlakshana and Schild, 1959) gave the pA2 values of PGE2, PGE1 and PGF2 alpha 4.90, 6.28 and 4.16, the slopes of the Schild plots being 1.05, 1.18 and 1.11 respectively. This suggests that SC-19220 is a competitive antagonist. Moreover, the antagonistic action of SC-19220 appeared to be a specific one since at concentrations of 3 X 10(-6) M to 3 X 10(-4) M the compound had a little, if any, effect on the responses of the gastric muscle to acetylcholine and histamine. This favors the suggestion that the longitudinal layer of the guinea-pig stomach contains prostaglandins receptors which are the same for PGE1, PGE2 and PGF2 alpha. SC-19220 specifically blocks these prostaglandin receptors characterized by the order of agonist potency PGE2 greater than PGE1 greater than PGF2 alpha.