[Effect of tranilast on the release of slow reacting substance of anaphylaxis (SRS-A) and contraction of the smooth muscle].

Abstract

Slow reacting substance of anaphylaxis (SRS-A) and slow reacting substance (SRS) were released from actively sensitized guinea-pig lung with bovine serum albumin and from rat peritoneal exudate cells with ionophore A23187, respectively. FPL55712 markedly inhibited the contraction induced by SRS-A and SRS in guinea-pig ileum which was treated with atropine (10(-7) g/ml), mepyramine (10(-6) g/ml), and cyproheptadine (10(-7) g/ml). Tranilast and isoproterenol markedly suppressed the release of SRS-A in a dose-dependent manner; the concentrations of these drugs that gave 50% inhibition (IC50) were 1.1 X 10(-4)M and 8.3 X 10(-9)M, respectively. Although the inhibitory effect of tranilast (10(-3)M) was not affected in the presence of propranolol (3 X 10(-6)M), the inhibitory effect of isoproterenol was greatly diminished by propranolol. Also, tranilast markedly suppressed the release of SRS in a dose-dependent manner, its IC50 being 6.4 X 10(-5)M. However isoproterenol slightly inhibited the release of SRS. Disodium cromoglycate did not suppressed the release of SRS-A at all, and it suppressed SRS release a little. Tranilast inhibited the contraction induced by leukotriene C4 (0.5 ng/ml) and D4 (1 ng/ml) in guinea-pig trachea in a dose-dependent manner; the IC50 values were 2.2 X 10(-4)M and 2.0 X 10(-4)M, respectively, for these inhibitions. These results suggest that the inhibition of SRS-A release and SRS-A-induced contraction of smooth muscle by tranilast participates in the anti-asthmatic effect of tranilast, and its inhibitory mechanism is different from that of isoproterenol.