Effect of endothelin-1 on corticosteroid secretion by the frog adrenal gland is mediated by an endothelin(A) receptor

We have previously reported that endothelin-l (ET-1) stimulates the in vitro secretion of corticosterone and aldosterone from the adrenal gland of the frog Rana ridibunda. The aim of the present study was to investigate the pharmacological profile of the endothelin receptor subtype involved in the corticotropic effect of ET-1. The mixed ETA/ETB receptor antagonist Ro 47-0203 (10(-5) M) totally blocked the stimulatory effect of ET-1 (5 x 10(-9) M) on corticosterone and aldosterone secretion. The action of ET-1 was also inhibited by the selective ETA receptor antagonist BQ-485 (10(-7) M). In contrast, the selective ETB receptor antagonist IRL 1038 (10(-6) M) did not affect the response of the frog adrenal gland to ET-1. In addition, the selective ETB receptor agonist IRL 1620 (10(-6) M) did not mimic the stimulatory effect of ET-1. The high affinity ETC receptor agonist endothelin-3 (ET-3) stimulated corticosteroid secretion, but was 400 times less potent than ET-1. Moreover, the action of ET-3 was also blocked by BQ-485 (10(-7) M). These data indicate that the stimulatory effects of ET-1 and ET-3 on corticosteroid secretion by the frog adrenal gland are mediated by an ETA receptor subtype.