Endothelin adrenocortical secretagogue effect is mediated by the B receptor in rats

We investigated the gene expression and localization of endothelin-1 (ET-1) receptor subtypes ET(A) and ET(B) in the rat adrenal cortex as well as their involvement in the corticosteroid secretagogue effect of ET-1 in vitro. Reverse transcription-polymerase chain reaction with primers specific for ET(A) and ET(B) cDNAs demonstrated the expression of 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 displacement of 125I-ET-1 binding by BQ-123 and BQ-788 (specific ligands for ET(A) and ET(B), respectively) indicated that zona glomerulosa possesses both ET(A) and ET(B), whereas zona fasciculata is exclusively provided with ET(B). ET-1 enhanced in a concentration-dependent manner aldosterone 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 ET(B) receptor subtype and that the ET(A) receptor is not directly involved in such an effect.