The role of the diacylglycerol-protein kinase C system in mediating adrenoceptor-prostacyclin synthesis coupling in the rat aorta

The role of the diacylglycerol-protein kinase C system in mediating adrenoceptor-stimulated prostacyclin (PGI₂) synthesis in the isolated rat aorta was investigated using the diacylglycerol-mimetic phorbol 12,13-dibutyrate (PDBU) and the protein kinase C inhibitor 1-(5-isoquinolinylsulfonyl)-2-methylpiperizine (H7). PDBU stimulated rat aortic PGI₂ synthesis in a dose-dependent manner, an action potentiated by adrenaline and the calcium ionophore A23187. EDTA (10^-2 mol·1^-1) completely inhibited PDBU-stimulated PGI₂ synthesis. The calcium channel blockers, verapamil and nifedipine, inhibited PDBU-stimulated PGI₂ synthesis in a dose-dependent manner, as did the protein kinase C inhibitor H7. The adrenoceptor antagonists phentolamine, prazosin and yohimbine were without effect on PDBU-stimulated PGI₂ synthesis. H7 also inhibited adrenaline-stimulated, but not trauma-, A23187- or arachidonate-stimulated PGI₂ synthesis. These experiments constitute evidence that adrenoceptor-PGI₂ synthesis coupling is mediated by diacylglycerol-protein kinase C initiation of calcium influx in the rat aorta.