IN-VITRO AUTORADIOGRAPHIC DEMONSTRATION OF ENDOTHELIN-1 BINDING-SITESIN 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 E T-1 receptors have been recently identified: ET(A) and ET(B), which ar e expressed by vascular smooth-muscle cells and endothelium, respectiv ely. Compelling evidence indicates that ET-1 exerts a strong secretago gue 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 i t was clearly confined to the endothelial lining of capillaries. BQ-12 3, a selective antagonist of ET(A), markedly attenuated I-125-ET-1. la beling 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 Z F. In light of these findings the conclusion is drawn that human ZG pa renchymal cells possess specific ET-1 receptors, being probably able t o express both ET(A) and ET(B) receptor subtypes.