EFFECT OF THE SEROTONIN-4 RECEPTOR AGONIST ZACOPRIDE ON ALDOSTERONE SECRETION FROM THE HUMAN ADRENAL-CORTEX - IN-VIVO AND IN-VITRO STUDIES

We have recently shown that serotonin (5-HT) stimulates cortisol secre tion from human adrenocortical tissue in vitro through activation of 5 -HT4 receptors. The aim of the present study was to investigate the ef fect of the 5-HT4 agonist racemic zacopride on aldosterone secretion f rom the human adrenal gland in vivo and in vitro. In vivo studies were conducted on 28 healthy volunteers pretreated with dexamethasone. The subjects received a single oral dose of placebo, 10 mu g zacopride, o r 400 mu g zacopride. Plasma aldosterone levels increased significantl y within 90 min after the administration of 400 mu g zacopride, remain ed elevated for 60 min, and gradually returned to the baseline within 180 min. In contrast, the administration of 10 mu g zacopride or place bo did not modify the aldosterone concentration. No significant change s were observed in renin, ACTH, or cortisol levels. In vitro studies w ere conducted on perifused human adrenocortical slices. Administration of 20-min pulses of zacopride (from 10(-11)-10(-6) mol/L) induced a d ose-dependent increase in aldosterone secretion. The minimal effective dose was 10(-10) mol/L, and half-maximal stimulation was obtained wit h a dose of 7 x 10(-8) mol/L. Zacopride was 100 times more potent in s timulating aldosterone than cortisol release. Taken together, the pres ent data suggest that 5-HT-evoked aldosterone secretion involves the a ctivation of 5-HT4 receptors.