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 × 10^-3 mol·1^-1), an action inhibited completely by the presence of EDTA (10^-2 mol·1^-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 × 10^-3 mol· 1^-1) PGI₂ sythesis 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.