ETA Receptors Mediate Activation of Phospholipases C and D In Rat Myometrium

In estrogen-treated rat myometrium, endothelial (ET-1) activated both the phospholipase C (PLC) which degrades PtdInsP2, resulting in an increased accumulation of inositol phosphates, and the phospholipase D pathway (PLD) as evidenced in the presence of butanol by an increased production of phosphatidylbutanol (PBut). Both ET-1 effects displayed similar concentration dependencies (EC50 50 nM) and were mediated by ETA receptors in that they were antagonized by BQ123 and were elicited by ET-3 with a rank order of potency ET-1 < ET-3. Bombesin, another activator of the PLC/ PtdInsP2 pathway, also increased PBut accumulation. Enhanced production of PBut could also be observed with the Ca ionophore ionomycin and the phorbol ester PMA, an activator of protein kinase C, suggesting a potential contribution of the PLC/PtdInsP2 pathway in ET-1 induced PLD activity.