INHIBITION BY PROTEIN-KINASE-C ACTIVATION OF MELITTIN-INDUCED ARACHIDONIC-ACID RELEASE IN PC12 PHEOCHROMOCYTOMA CELLS

In rat PC12 pheochromocytoma cells, melittin, a phospholipase A2 activator, stimulated the release of arachidonic acid in a dose-dependent manner in the range between 0.1 and 1 muM. 12-O-Tetra-decanoylphorbol-13-acetate TPA). a protein kinase C-activating phorbol ester, inhibited the melittin-induced release of arachidonic acid dose-dependently in the range between 0.1 nM and 0.1 muM, whereas 4alpha-phorbol 12, 13-didecanoate, which is inactive for protein kinase C, was ineffective in this capacity. Staurosporine, a protein kinase C inhibitor, recovered the inhibitory effect of TPA on the melittin-induced release of arachidonic acid. These results suggest that the activation of protein kinase C inhibits phospholipase A2 activity in PC 12 pheochromocytoma cells.