ET(A) RECEPTORS MEDIATE ACTIVATION OF PHOSPHOLIPASE-C AND PHOSPHOLIPASE-D IN RAT MYOMETRIUM

In estrogen-treated rat myometrium, endothelin-1 (ET-1) activated both the phospholipase C (PLC) which degrades PtdInsP(2), 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 (EC(50) 50 nM) and were mediated b y ET(A) receptors in that they were antagonized by BQ123 and were elic ited by ET-3 with a rank order of potency ET-1 much greater than ET-3. Bombesin, another activator of the PLC/PtdInsP(2) pathway, also incre ased PBut accumulation. Enhanced production of PBut could also be obse rved with the Ca2+ ionophore ionomycin and the phorbol ester PMA, an a ctivator of protein kinase C, suggesting a potential contribution of t he PLC/PtdInsP(2) pathway in ET-1 induced PLD activity.