Arachidonic Acid is Involved in Catecholamine Release Mechanism of PGE₂ in Bovine Adrenal Chromaffin Cells

Abstract

We recently reported that both prostaglandin E₂ (PGE₂) and arachidonic acid (AA) in the presence of ouabain induced a gradual secretion of catecholamines from cultured bovine adrenal chromaffin cells by stimulation of phosphoinositide metabolism. Because AA is a precursor of PGE₂, we examined the relationship between PGE₂- and AA-induced catecholamine release from the cells. No inhibitors of cyclooxygenase or lipoxygenase enzymes prevented phosphoinositide metabolism evoked by AA. On the other hand, PGE₂ induced rapid hydrolysis of [³H]AA from prelabeled phospholipid pools: the release of [³H]AA could be detected at as early as 15 sec and reached a plateau after 1 min. While phospholipase A₂ inhibitors p-bromophenacyl bromide and mepacrine inhibited PGE₂-induced AA release, the phospholipase C inhibitor neomycin did not inhibit it. These phospholipase inhibitors blocked PGE₂-evoked catecholamine release as well as stimulation of phosphoinositide metabolism. Pretreatment of intact cells with the phorbol ester TPA prevented activation of phospholipase A₂ and phospholipase C by PGE₂. These results demonstrate that PGE₂ induces AA release via direct activation of phospholipase A₂ and that the released AA may be involved in PGE₂-induced catecholamine release from chromaffin cells.