ENDOTHELIN-1 MODULATES RENIN AND PROLACTIN-RELEASE FROM HUMAN DECIDUABY DIFFERENT MECHANISMS

Endothelin (ET)-1 stimulates the synthesis and release of renin and in hibits the expression of prolactin (PRL) from term human decidual cell s. To examine the mechanisms by which ET-1 exerts its differential eff ects 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 potentia ted ET-1-stimulated renin release but had no effect on basal or ET-inh ibited PRL release. The calcium channel blocker nifedipine inhibited E T-1-stimulated renin release but had no effect on PRL release. The pro tein kinase C agonist phorbol 12-myristate 13-acetate (PMA) stimulated basal renin release and potentiated the effect of ET-1 on renin relea se. However, PMA inhibited basal PRL release and also enhanced the inh ibitory effect of ET-1. The PKC inhibitor staurosporine increased basa l PRL release and completely reversed the inhibitory effect of ET on P RL release. These results indicate that the effects of ET-1 on both de cidual renin and PRL release are dependent on the activation of protei n 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.