Fluoride stimulates in vitro vascular prostacyclin synthesis: interrelationship of G proteins and protein kinase C.
The role of G proteins in mediating adrenoceptor-prostacyclin synthesis coupling was investigated using the G protein activator, sodium fluoride. Sodium fluoride (NaF) stimulated in vitro rat aortic prostacyclin (PGI2) synthesis (EC50 = 5 x 10(-3) mol.l-1), an action inhibited completely by the presence of EDTA (10(-2) mol.l-1). The NaF-PGI2 dose-response curve was moved to the left by the presence of adrenaline, phorbol 12,13-dibutyrate (PDBU) and the Ca2+ ionophore A23187 in the incubation media. NaF-stimulated (5 x 10(-3) mol.l-1) PGI2 synthesis was inhibited by the Ca2+ channel blockers, verapamil and nifedipine, the protein kinase C inhibitor, H7, and lanthanum. Prazosin and yohimbine were without effect on NaF action, but partially inhibited adrenaline-potentiated NaF-stimulated PGI2 synthesis. Cyclic adenosine-3',5'-monophosphate (cAMP) and dibutyryl cAMP were without effect on de novo or NaF-, adrenaline-, PDBU- or A23187-stimulated PGI2 synthesis. Since fluoride is known to stimulate adenyl cyclase and phospholipase C, these data suggest that: (1) NaF stimulates in vitro rat aortic PGI2 synthesis by initiating Ca2+ influx; (2) this Ca2+ influx is mediated by protein kinase C, probably through G protein activation of phospholipase C and the generation of the protein kinase C activator, diacyl glycerol; and (3) adenyl cyclase and protein kinase A are not involved in NaF-stimulated PGI2 synthesis by the rat aorta.
D000818:Animals; D001011:Aorta / Q000378:metabolism; D000001:Calcimycin / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004492:Edetic Acid / Q000494:pharmacology; D004789:Enzyme Activation; D004837:Epinephrine / Q000494:pharmacology; D011464:Epoprostenol / Q000096:biosynthesis*; D066298:In Vitro Techniques; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000502:physiology*; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D011919:Rats, Inbred Strains; D012969:Sodium Fluoride / Q000037:antagonists & inhibitors / Q000494:pharmacology*
D002121:Calcium Channel Blockers; C029152:G-substrate; D009419:Nerve Tissue Proteins; D010703:Phorbol Esters; D015240:Phorbol 12,13-Dibutyrate; D000001:Calcimycin; D012969:Sodium Fluoride; D004492:Edetic Acid; D011464:Epoprostenol; D011493:Protein Kinase C; D004837:Epinephrine