Pardaxin Stimulation of Phospholipases A2 and Their Involvement in Exocytosis in PC-12 Cells

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 A2 inhibitors we show that PX stimulation of phospholipase A2 (PLA2) enzymes is coupled with induction of exocytosis. We investigated the relationship between PX-induced PLA2 activity and neurotransmitter re-lease by measuring the levels of arachidonic acid (AA), prosta-glandin E2 (PGE2), and dopamine release. In the presence of extracellular calcium, the cytosolic PLA2 inhibitor arachidonyl trifluoromethyl ketone (AACOCF3) inhibited by 100, 70, and 73%, respectively, the release of AA, PGE2, and dopamine induced by PX. The mitogen-activated protein kinase/extracel-lular signal-regulated kinase inhibitor 2-amino-3-methoxyfla