PHOSPHOLIPASE A₂ ACTIVITY OF GUINEA‐PIG ISOLATED PERFUSED LUNGS: STIMULATION, AND INHIBITION BY ANTI‐INFLAMMATORY STEROIDS

Abstract

A simple double‐isotope assay for phospholipase A 2 activity of perfused organs is described. Guinea‐pig lungs perfused through the pulmonary circulation exhibit a low background enzyme activity. This activity is blocked by dexamethasone, betamethasone and hydrocortisone, mepacrine, procaine or chlorpromazine. Aspirin and indomethacin are without effect. Mechanical trauma, antigen challenge or injections of bradykinin, rabbit aorta contracting substance‐releasing factor (RCS‐RF) or histamine increase ‘basal’ phospholipase activity. The effect of these agents, except that of bradykinin, is blocked by dexamethasone or mepacrine. The blocking effect of steroids is cumulative and dose‐dependent. They do not work in cell‐free systems. Inhibition by mepacrine is rapid and is effective in cell‐free lung homogenates. It is suggested that agents which liberate prostaglandin endoperoxides and thromboxane A 2 from perfused lungs do so by activating phospholipase A 2 .