Pardaxin Stimulation of Phospholipases A 2 and Their Involvement in Exocytosis in PC-12 Cells

Abstract

Pardaxin (PX) is a voltage-dependent ionophore that stimulates catecholamine exocytosis from PC-12 pheochromocytoma cells both in the presence and absence of extracellular calcium. Using a battery of phospholipase A 2 inhibitors we show that PX stimulation of phospholipase A 2 (PLA 2) enzymes is coupled with induction of exocytosis. We investigated the relationship between PX-induced PLA 2 activity and neurotransmitter release by measuring the levels of arachidonic acid (AA), prostaglandin E 2 (PGE 2), and dopamine release. In the presence of extracellular calcium, the cytosolic PLA 2 inhibitor arachidonyl trifluoromethyl ketone (AACOCF 3) inhibited by 100, 70, and 73%, respectively, the release of AA, PGE 2, and dopamine induced by PX. The mitogen-activated protein kinase/extracellular signal-regulated kinase inhibitor 2�-amino-3�-methoxyflavon