LACK OF EFFECT OF THE SEROTONIN(4) RECEPTOR AGONIST ZACOPRIDE ON ACTH-SECRETION IN NORMAL MEN

Objective: In the present study, we investigated the effect of zacopri de on corticotropin (ACTH) and cortisol secretion in healthy volunteer s. Male subjects received a single oral dose of placebo, 10 mu g zacop ride or 400 mu g zacopride. Plasma ACTH, cortisol and aldosterone conc entrations were measured before and during the 3 h following the admin istration of the drug. Results: For none of the doses did zacopride ca use any modification of plasma ACTH or cortisol levels, In contrast, a dministration of 400 mu g zacopride induced a significant increase in plasma aldosterone levels. Conclusion: Our results indicate that in hu mans serotonin-evoked stimulation of ACTH secretion is not mediated th rough serotonin(4) (5-HT4) receptors. Together with previous findings, these data indicate that the stimulatory effect of 5-HT4 receptor ago nists on aldosterone secretion in man can be ascribed solely to a dire ct action on glomerulosa cells.