The release and metabolism of [3H]arachidonic acid from guinea pig perfused lungs in vitro: a simple method for the study of the action of drugs on the release and metabolism of arachidonic acid.

We have adapted the radiolabeled, perfused organ technique of Isakson et al. (1976) for use with guinea pig lungs. After incorporation [3H]arachidonic acid was taken up into the lung phospholipids. The injection of bradykinin (1-100 microgram) caused a dose-related release of tritium [3H]. The composition of the tritium released by the lungs was found to be a mixture of cyclo-oxygenase and lipoxygenase metabolites together with some unchanged arachidonic acid. In order to demonstrate how this technique can be utilized to study the effect of drugs on arachidonic acid release and metabolism, the actions of mepacrine and indomethacin on bradykinin-induced [3H] release were studied. Mepacrine (50-200 microM) produced a concentration-related reduction in bradykinin-induced [3H] release whereas indomethacin (10 microM) was without effect on [3H] release. Indomethacin did, however, reduce the levels of cyclo-oxygenase products in the perfusate.