Mechanism of inhibitory action of tranilast on the release of slow reacting substance of anaphylaxis (SRS-A) in vitro: effect of tranilast on the release of arachidonic acid and its metabolites.
We investigated the mechanism of inhibitory action of tranilast, one of the anti-allergic drugs, on the release of slow reacting substance of anaphylaxis (SRS-A). Ionophore A23187 (0.5 or 0.2 micrograms/ml)-induced SRS-A release from rat peritoneal exudate cells (PEC) or human leucocytes was inhibited by tranilast (10(-5)-10(-3) M). The IC50 (the concentration which gives 50% inhibition) of tranilast on these reactions was approx. 10(-4) M. Prostaglandin (PG)E2 release from sensitized purified rat mast cells (PMC) by a specific antigen (DNP-Ascaris) was markedly suppressed by tranilast (10(-3) M). Similarly, ionophore A23187-induced PGE2 and 6-keto-PGF1 alpha releases from rat PEC were inhibited by tranilast (10(-5)-10(-3) M). DNP-Ascaris antigen-induced 3H-arachidonic acid (AA), 3H-PGE2, 3H-PGF2 alpha and 3H-PGD2 releases from rat PMC were markedly suppressed by tranilast (10(-5)-10(-3) M), DSCG (10(-5)-10(-4) M) and mepacrine (10(-3) M). The activity of AA-converting enzymes such as 5-lipoxygenase, cyclooxygenase, PGI2 synthetase, and glutathione-S-transferase was hardly influenced by tranilast (10(-5)-10(-3) M). From these results, we suggest that the mechanism of the inhibitory action of tranilast on the release of SRS-A is related to the processes prior to dissociation of AA from the membrane phospholipids.
D000818:Animals; D001094:Arachidonate 5-Lipoxygenase / Q000378:metabolism; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D001241:Aspirin / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D006632:Histamine / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D051379:Mice; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D013189:SRS-A / Q000037:antagonists & inhibitors*; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D001095:Arachidonic Acids; D011453:Prostaglandins; D013189:SRS-A; D062367:ortho-Aminobenzoates; D016718:Arachidonic Acid; D000001:Calcimycin; D006632:Histamine; D001094:Arachidonate 5-Lipoxygenase; D011451:Prostaglandin-Endoperoxide Synthases; C012293:tranilast; D001241:Aspirin