EFFECT OF ARACHIDONIC-ACID ON HISTAMINE-INDUCED AND METHACHOLINE-INDUCED CONTRACTION OF THE ISOLATED GUINEA-PIG TRACHEAL CHAIN WITH AND WITHOUT EPITHELIAL-CELLS

The relaxant effect of exogenous arachidonic acid on histamine- and me thacholine-induced contraction was investigated and also the contribut ion of the epithelium and the role of synthesised prostaglandins by th e epithelium. The isolated tracheas of six guinea-pigs were used in ea ch experiment and suspended in organ baths filled with Krebs-Henseleit solution and gassed with 95% O-2 and 5% CO2. Arachidonic acid produce d a relaxation of 43.5 +/- 3.2% (3 x 10(-4) M) (p < 0.05) for methacho line-induced contraction and 60.7 +/- 0.2% (10(-5) M) (p < 0.05) for h istamine-induced contraction as compared to salbutamol in preparations with intact epithelium. Epithelium removal had opposite effects for t he different contractants. The relaxant effect of arachidonic acid aft er methacholine-induced contraction was increased, but the relaxant ef fect of arachidonic acid after histamine-induced contraction was decre ased. Indomethacin pre-incubation had no effect on the relaxant effect of arachidonic acid after methacholine-induced contraction, but the r elaxant effect of arachidonic acid was changed to contraction after hi stamine-induced contraction at concentrations of 10(-5) M and higher o f arachidonic acid. This occurred in preparations with intact epitheli um and with no epithelium. It is clear that the mechanism involved in the relaxant effect of arachidonic acid is complex and involves the pr oducts produced by the epithelial cells and the added effects induced by the specific contractant used.