The effect of inhibitors of arachidonic acid metabolism on drug-induced contractions in isolated tracheal smooth muscle of the pig.

Abstract

1 The regulation of drug-induced tone in airways smooth muscle was examined in an isolated preparation of swine tracheal smooth muscle. 2 The trachea contracted (isometric) to histamine, 2-pyridylethylamine (2-PEA), acetylcholine and K+ but no response to histamine H2-receptor agonists were observed. 3 Histamine-induced contractions (100 microM) were potentiated by 213.3% by indomethacin (1 microM) and by 126.9% by sodium salicylate (250 microM). These inhibitors had only slight or no effects on acetylcholine-induced tone. 2-PEA responses were also potentiated by indomethacin but there were no changes in the response to H2-receptor agonists in the presence of indomethacin. The indomethacin-mediated potentiation of histamine was blocked by 5, 8, 11, 14-eicosatetraynoic acid (10 microM). FPL 55712 had no effect on these responses. 4 Mepacrine (100 microM) inhibited responses to histamine but not those to acetylcholine. No effect was observed with dexamethasone (up to 100 microM). 5 Prostaglandin E2 caused relaxation but arachidonic acid did not. 6 The possibility that histamine H1-agonist-induced contractions are regulated by contractile products of the arachidonic acid lipoxygenase pathway is discussed.