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

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  • KOMATSU Hidetada
    Central Research Laboratories, Kissei Pharmaceutical Co., Ltd.
  • UJIIE Arao
    Central Research Laboratories, Kissei Pharmaceutical Co., Ltd.
  • NAITO Jun
    Central Research Laboratories, Kissei Pharmaceutical Co., Ltd.

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  • Ｓｌｏｗ　ｒｅａｃｔｉｎｇ　ｓｕｂｓｔａｎｃｅ　ｏｆ　ａｎａｐｈｙｌａｘｉｓ（ＳＲＳ‐Ａ）の遊離および平滑筋収縮に及ぼすＴｒａｎｉｌａｓｔの影響
  • Slow reacting substance of anaphylaxis

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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 (10-7g/ml), mepyramine (10-6g/ml), and cyproheptadine (10-7g/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 1.1×10-4M and 8.3×10-9M, respectively. Although the inhibitory effect of tranilast (10-3M) was not affected in the presence of propranolol (3×10-6M), 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 6.4×10-5M. 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 2.2×10-4M and 2.0×10-4M, 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.

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