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 activation of 5-HT4 receptors coupled to adenylyl cyclase via a Gs regulatory protein. In adrenocortical cells, the levels of expression of the Gs 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 ANG II on the responsiveness of human glomerulosa cells to 5-HT, we have investigated the effect of cisapride, a 5-HT4 receptor agonist, on plasma aldosterone in patients with suppressed plasma ACTH, i.e. patients with corticotropic insufficiency (CI), and in patients with suppressed renin-ANG II activity, i.e. patients with primary hyperaldosteronism (PH) including both aldosterone-producing adenoma and idiopathic hyperaldosteronism. After 2 h of recumbency, all patients received a single oral dose of 10 mg cisapride. In the CI group, cisapride induced a 5-fold increase in plasma aldosterone levels without any modification of plasma renin, potassium or cortisol levels. Combined administration of cisapride and ACTH caused an increase in plasma aldosterone similar to that produced by ACTH alone. In the PH group, cisapride was still able to cause a 3.6-fold increase in plasma aldosterone levels while renin remained suppressed throughout the study. Taken together, these data show that cisapride stimulates aldosterone secretion in CI and PH patients, indicating that prolonged suppression of plasma ACTH or renin-ANG II activity does not affect the sensitivity of glomerulosa cells to 5-HT. The present study also demonstrates that the stimulatory effects of 5-HT and ACTH on aldosterone secretion are not additive.
Lefebvre
H
H
European Institute for Peptide Research (IFRMP 23), Group for Hormone Research, CHU, Rouen, France.
Dhib
M
M
Godin
M
M
Contesse
V
V
Delarue
C
C
Rieu
M
M
Wolf
L M
LM
Vaudry
H
H
Kuhn
J M
JM
D000324:Adrenocorticotropic Hormone / Q000097:blood / Q000172:deficiency* / Q000494:pharmacology; D000328:Adult; D000450:Aldosterone / Q000378:metabolism*; D000804:Angiotensin II / Q000097:blood / Q000494:pharmacology; D020117:Cisapride; D005260:Female; D006801:Humans; D006929:Hyperaldosteronism / Q000188:drug therapy*; D008297:Male; D008875:Middle Aged; D010880:Piperidines / Q000627:therapeutic use*; D012083:Renin / Q000097:blood; D012636:Secretory Rate / Q000187:drug effects; D017366:Serotonin Receptor Agonists / Q000627:therapeutic use*; D015384:Zona Glomerulosa / Q000166:cytology / Q000187:drug effects
D010880:Piperidines; D017366:Serotonin Receptor Agonists; D000804:Angiotensin II; D000450:Aldosterone; D000324:Adrenocorticotropic Hormone; D012083:Renin; D020117:Cisapride