Effect of prolonged administration of the serotonin4 (5-HT4) receptor agonist cisapride on aldosterone secretion in healthy volunteers.
In man, serotonin (5-HT) has been shown to stimulate aldosterone secretion through activation of 5-HT4 receptors, In particular, we have observed that oral administration of a single dose of the 5-HT4 receptor agonist cisapride (10 mg) induces a 5-fold increase in plasma aldosterone levels in healthy volunteers. Surprisingly, the usual disorders associated with hyperaldosteronism, i.e. hypertension and hypokalemia, have never been reported during chronic treatment with cisapride. In the present study, we have investigated the effect of prolonged oral administration of cisapride (10 mg, 3 times/day during 7 days) on aldosterone secretion in 12 healthy volunteers, in a simple blind fashion versus placebo. On day 1 of the treatment, cisapride induced a significant increase in plasma aldosterone levels (PAL) which returned to the values observed after placebo treatment within 10 hrs. On days 2 and 3, PAL were similar in cisapride- and placebo-treated subjects. Urinary aldosterone, kalemia and reninemia were not influenced by cisapride during the 7 days of the treatment. The present study shows that cisapride only exerts a transient stimulatory effect on aldosterone secretion in healthy volunteers. These data explain why long-term administration of 5-HT4 agonists does not affect blood pressure in man. They also indicate that prolonged stimulation of adrenal 5-HT4 receptors in vivo yields to a rapid desensitization phenomenon, as previously observed in vitro.
Lefebvre
H
H
European Institute for Peptide Research (IFRMP no 23), Department of Endocrinology and Metabolic Diseases, CHU of Rouen, France.
Gonzalez
K N
KN
Contesse
V
V
Delarue
C
C
Vaudry
H
H
Kuhnl
J M
JM
D000450:Aldosterone / Q000097:blood*; D020117:Cisapride / Q000008:administration & dosage* / Q000494:pharmacology; D006801:Humans; D009318:Natriuresis / Q000187:drug effects; D012016:Reference Values; D017366:Serotonin Receptor Agonists / Q000008:administration & dosage* / Q000494:pharmacology; D013997:Time Factors
D017366:Serotonin Receptor Agonists; D000450:Aldosterone; D020117:Cisapride