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 gl and of the frog Rana ridibunda. The aim of the present study was to in vestigate the pharmacological profile of the endothelin receptor subty pe involved in the corticotropic effect of ET-1. The mixed ETA/ETB rec eptor antagonist Ro 47-0203 (10(-5) M) totally blocked the stimulatory effect of ET-1 (5 x 10(-9) M) on corticosterone and aldosterone secre tion. The action of ET-1 was also inhibited by the selective ETA recep tor antagonist BQ-485 (10(-7) M). In contrast, the selective ETB recep tor 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 ag onist IRL 1620 (10(-6) M) did not mimic the stimulatory effect of ET-1 . The high affinity ETC receptor agonist endothelin-3 (ET-3) stimulate d corticosteroid secretion, but was 400 times less potent than ET-1. M oreover, the action of ET-3 was also blocked by BQ-485 (10(-7) M). The se data indicate that the stimulatory effects of ET-1 and ET-3 on cort icosteroid secretion by the frog adrenal gland are mediated by an ETA receptor subtype.