Endothelin ETA receptors subtype mediates phosphoinositide hydrolysis in adrenal medulla

We investigated the effect of endothelins (ETs) on receptor-mediated phosphoinositide turnover in whole adrenal medulla. Endothelin -1, -2, -3 increased phosphoinositide (PI) turnover by 30% in whole adrenal medulla prelabeled with (3H)myoinositol. ET-stimulation of PI hydrolysis was almost completely dependent on the presence of the extracellular calcium since its chelation resulted in a blockade of ETs induced InsP1 accumulation. Addition of cadmium increased basal and ETs-stimulated InsP1 accumulation. ETs induced InsP1 accumulation was inhibited by BQ 123, a selective antagonist of the ETA receptor, while BQ 788, a selective antagonist of the ETB receptor, was ineffective. The selective agonist at the endothelin ETB receptor, IRL 1620, was ineffective to induce changes in inositide metabolism. Our data indicate that stimulation of PI turnover constitutes one of the signalling pathways of ETs in rat adrenal medulla and that this action is mediated through ETA receptor activation. These results suggest that endothelin could play a role in the regulation of adrenal medulla function.