Signaling mechanisms induced by endothelin agonists in human adrenal glomerulosa cells

Endothelin-1 (ET-1) exhibits secretagogue and trophic actions on the adrenal zona glomerulosa (ZG). Little information is available on the intracellular signaling events that follow stimulation of ET receptors on ZG cells. This study examined the expression of ET receptor subtypes and their involvement in transduction mechanisms induced by ET agonists on human ZG cells in primary culture. RT-PCR allowed the detection of both ETA and ETB receptor mRNAs in these cells. ET-1 induced a concentration-dependent increase in inositol phosphate (IP) accumulation in the presence of LiCl, whereas ETB agonists were inactive. The ET-1-induced increase in IP accumulation was prevented by BQ-123. ET-1 evoked an increase in [Ca2+]i, which was partially prevented by BQ-788. IRL 1620 also delayed the rise in [Ca2+]i. These results show that in human adrenal ZG cells, ET-1 induces an increase in IP accumulation through ETA receptor activation and evokes a rise in [Ca2+]i via stimulation of both ETA and ETB receptors.