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Endothelin Stimulates Steroid Secretion by Frog Adrenal Gland in Vitro : Evidence for the Involvement of Prostaglandins and Extracellular Calcium in the Mechanism of Action of Endothelin*

1990; Oxford University Press; Volume: 127; Issue: 4 Linguagem: Inglês

10.1210/endo-127-4-2001

1945-7170

Catherine Delarue, Isabelle Delton, Ferdinando Fiorini, Françoise Homo‐Delarche, Aldo Fasolo, P. Braquet, Hubert Vaudry,

Neuropeptides and Animal Physiology

Endothelin (ET-1) is a pleiotropic regulatory peptide which exerts multiple endocrine actions on the cardiovascular system. In the present study, we have investigated the possible role of ET-1 in the regulation of adrenocortical cells using perifused frog interrenal (adrenal) slices. Graded doses of ET-1 from 10-11-10-9 M stimulated both corticosterone and aldosterone production in a dose-dependent manner. Repeated 20-min pulses of ET-1 (10-9 M), given at the frequency of one pulse per 90 min, resulted in a marked reduction of the secretory response after the second pulse. Prolonged administration (3 h) of ET-1 induced a rapid increase in corticosterone and aldosterone output, followed by a gradual decline of corticosteroid secretion. Perifusion of frog adrenal tissue with ET-1 (10-9 M) caused a significant increase in the release of prostaglandin E2 (PGE2) and 6-keto-PGF1α the stable metabolite of the prostacyclin PGI2. The enhancement of PG biosynthesis preceded by 10 min the peak of corticosteroids. When repeated pulses of ET-1 were administered, a significant diminution of the production of PGE2 and 6-keto-PGFlα was observed after the second pulse. The cyclooxygenase inhibitor indomethacin (5 μM) totally suppressed the stimulatory effect of ET-1 on corticosterone and aldosterone secretion; in contrast, indomethacin did not affect ACTHevoked corticosteroid secretion. Perifusion of adrenal slices with a calcium-free solution or addition of cobalt (4 mM) induced total inhibition of the stimulatory effect of ET-1. These results demonstrate that ET-1 is a potent stimulator of corticosterone and aldosterone secretion from frog adrenal gland in vitro. Our data show that repeated or prolonged administration of ET-1 induces a rapid desensitization phenomenon. The data also indicate that ET-1-evoked corticosteroid secretion is mediated by an increase in PG biosynthesis and requires the presence of extracellular calcium. (Endocrinology127: 2001–2008, 1990)