MEDIATED BY THE B-RECEPTOR IN RATS

We investigated the gene expression and localization of endothelin-l ( ET-1) receptor subtypes ET(A) and ET(B) in the rat adrenal cortex as w ell as their involvement in the corticosteroid secretagogue effect of ET-1 in vitro. Reverse transcription-polymerase chain reaction with pr imers specific for ET(A) and ET(B) cDNAs demonstrated the expression o f both receptor genes in homogenates of adrenocortical tissue. However , in isolated zona glomerulosa and zona fasciculata cells, only ET(B) mRNA was detected. Autoradiographic examination of the selective displ acement of I-125-ET-1 binding by BQ-123 and BQ-788 (specific ligands f or ET(A) and ET(B), respectively) indicated that zona glomerulosa poss esses both ET(A) and ET(B), whereas zona fasciculata is exclusively pr ovided with ET(B). ET-1 enhanced in a concentration-dependent manner a ldosterone and corticosterone secretions of dispersed zona glomerulosa and zona fasciculata cells, respectively. The ET(B) antagonist BQ-788 markedly reduced the secretory response of zona glomerulosa cells and completely suppressed that of zona fasciculata cells, whereas the ET( A) antagonist BQ-123 was ineffective. These findings indicate that in the rat, the adrenocortical secretagogue action of ET-1 is mediated by the ETB receptor subtype and that the ET(A) receptor is not directly involved in such an effect.