Role for protein kinase C in A23187 induced glomerular arachidonate release and PGE2 production

A high concentration of the calcium ionophore A23187 (10 uM) stimulated release of labeled arachidonate and immunoreactive PGE2 from isolated superfused glomeruli. A lower concentration of A23187 (1 uM) or 12-0-tetradecanoyl phorbol-13-acetate (TPA, 0.1 uM), a direct activator of protein kinase C, when added alone was without effect on these parameters. Combined addition of A23187 (1 uM) and TPA (0.1 uM) synergistically stimulated arachidonate release and PGE2 production. 1-(5-isoquinolinyl)-2-methylpiperazine (H-7) a known inhibitor of protein kinase C in other tissues, suppressed increases in arachidonate release and PGE2 production mediated by A23187 (10 uM) or TPA plus A23187 (1 uM). H-7 inhibited while TPA stimulated protein kinase C activity that had been partially purified from soluble fractions of glomerular homogenates. These results support a role for protein kinase C in A23187 mediated arachidonate release.