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 X l-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.
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000818:Animals; D001013:Aorta, Thoracic / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004075:Diglycerides / Q000378:metabolism*; D004837:Epinephrine / Q000494:pharmacology; D011464:Epoprostenol / Q000096:biosynthesis*; D005989:Glycerides / Q000378:metabolism*; D066298:In Vitro Techniques; D007546:Isoquinolines / Q000494:pharmacology; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000378:metabolism*; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000494:pharmacology; D010879:Piperazines / Q000494:pharmacology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D011941:Receptors, Adrenergic / Q000378:metabolism*
D002121:Calcium Channel Blockers; D004075:Diglycerides; D005989:Glycerides; D007546:Isoquinolines; D010703:Phorbol Esters; D010879:Piperazines; D011941:Receptors, Adrenergic; D015240:Phorbol 12,13-Dibutyrate; D000001:Calcimycin; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D011464:Epoprostenol; D011493:Protein Kinase C; D002118:Calcium; D004837:Epinephrine