Endothelin Adrenocortical Secretagogue Effect Is Mediated by the B Receptor in Rats

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Abstract
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 125 I–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.