The stimulatory effect of endothelin-1 on frog adrenocortical cells is mediated through both the phospholipase C and the adenylyl cyclase transduction pathways

We have previously shown that endothelin-l (ET-1) stimulates corticosterone and aldosterone secretion by the frog adrenal gland through activation of ETA receptors. In the present study, we have investigated the transduction pathways involved in the corticotropic action of ET-I. Exposure of frog adr enal explants to ET-1 provoked a time- and dose-dependent increase in inosi tol phosphate production and a parallel decrease in membrane polyphosphoino sitide content. Incubation of adrenal explants with ET-l also induced a dos e-related increase of cAMP formation. The selective ETA receptor antagonist BQ-485 totally abolished the stimulatory effects of ET-1 on both inositol phosphate and cAMP production. In contrast, the selective ETB receptor agon ist IRL 1620 did not significantly modify polyphosphoinositide hydrolysis o r cAMP formation. Administration of the phospholipase C inhibitor U-73122 o r the protein kinase A inhibitor H-89 to perifused frog adrenal slices sign ificantly reduced the stimulatory effect of ET-I on corticosterone and aldo sterone secretion. Concomitant administration of the two inhibitors almost completely suppressed the corticotropic effect of ET-I. Taken together, the se data indicate that, in the frog adrenal gland, the stimulatory effect of ET-1 on corticosteroid secretion is mediated through activation of both th e phospholipase C and the adenylyl cyclase transduction pathways. (C) 1999 Elsevier Science Ireland Ltd. All rights reserved.