IN-VITRO AUTORADIOGRAPHIC DEMONSTRATION OF ENDOTHELIN-1 BINDING-SITES IN THE HUMAN ADRENAL-CORTEX

Endothelin-1 (ET-1) is a 21-amino acid peptide secreted by endothelial cells, that exerts a potent vasoconstrictor action. Two subtypes of ET-1 receptors have been recently identified: ET(A) and ET(B), which are expressed by vascular smooth-muscle cells and endothelium, respectively. Compelling evidence indicates that ET-1 exerts a strong secretagogue effect on adrenal zona glomerulosa (ZG), but not zona fasciculata (ZF) in vivo and in vitro; therefore, we performed an autoradiographic study of the occurrence of ET-1 receptors in the human adrenal cortex. I-125-ET-1 binding was intense in the ZG and weak in the ZF, where it was clearly confined to the endothelial lining of capillaries. BQ-123, a selective antagonist of ET(A), markedly attenuated I-125-ET-1. labeling in ZG, without affecting that in ZF; conversely, sarafotoxin 6C, a selective ligand of ET(B), caused a moderate attenuation of I-125-ET-1 binding in the ZG and, as expected, completely eliminated it in ZF. In light of these findings the conclusion is drawn that human ZG parenchymal cells possess specific ET-1 receptors, being probably able to express both ET(A) and ET(B) receptor subtypes.