EFFECT OF THE SEROTONIN 5-HT4 RECEPTOR AGONIST CISAPRIDE ON ALDOSTERONE SECRETION IN CORTICOTROPIC INSUFFICIENCY AND PRIMARY HYPERALDOSTERONISM

Serotonin (5-HT) stimulates aldosterone secretion in man through activ ation of 5-HT4 receptors coupled to adenylyl cyclase via a Gs regulato ry protein. In adrenocortical cells, the levels of expression of the G s protein and ACTH receptor are decreased when the cells are deprived of ACTH and angiotensin II (ANG II). In order to examine the possible influence of ACTH and ANC II on the responsiveness of human glomerulos a cells to 5-HT, we have investigated the effect of cisapride, a 5-HT4 receptor agonist, on plasma aldosterone in patients with suppressed p lasma ACTH, i.e. patients with corticotropic insufficiency (CI), and i n patients with suppressed renin-ANG II activity, i.e. patients with p rimary hyperaldosteronism (PK) including both aldosterone-producing ad enoma and idiopathic hyperaldosteronism. After 2 h of recumbency, all patients received a single oral dose of 10 mg cisapride. In the CI gro up, cisapride induced a 5-fold increase in plasma aldosterone levels w ithout any modification of plasma renin, potassium or cortisol levels. Combined administration of cisapride and ACTH caused an increase in p lasma aldosterone similar to that produced by ACTH alone. In the PH gr oup, cisapride was still able to cause a 3.6-fold increase in plasma a ldosterone levels while renin remained suppressed throughout the study . Taken together, these data show that cisapride stimulates aldosteron e secretion in CI and PH patients, indicating that prolonged suppressi on of plasma ACTH or renin-ANG II activity does not affect the sensiti vity of glomerulosa cells to 5-HT. The present study also demonstrates that the stimulatory effects of 5-HT and ACTH on aldosterone secretio n are not additive.