Endothelin-1 modulates renin and prolactin release from human decidua by different mechanisms

Endothelin (ET)-1 stimulates the synthesis and release of renin and inhibits the expression of prolactin (PRL) from term human decidual cells. To examine the mechanisms by which ET-1 exerts its differential effects on renin and PRL expression, we have studied total renin and PRL release from term human decidual cells in response to pharmacological agents that affect calcium- and protein kinase C-dependent mechanisms. Calcium ionophore A-23187 stimulated basal renin release and potentiated ET-1-stimulated renin release but had no effect on basal or ET-inhibited PRL release. The calcium channel blocker nifedipine inhibited ET-1-stimulated renin release but had no effect on PRL release. The protein kinase C agonist phorbol 12-myristate 13-acetate (PMA) stimulated basal renin release and potentiated the effect of ET-1 on renin release. However, PMA inhibited basal PRL release and also enhanced the inhibitory effect of ET-1. The PKC inhibitor staurosporine increased basal PRL release and completely reversed the inhibitory effect of ET on PRL release. These results indicate that the effects of ET-1 on both decidual renin and PRL release are dependent on the activation of protein kinase C. However, the effect of ET-1 on renin release appears to be dependent on extracellular calcium, whereas the effect on PRL is not influenced by extracellular calcium.