Evidence for a role of a serum factor stimulated by metoclopramide in regulating aldosterone secretion

The stimulatory effect of metoclopramide upon aldosterone secretion is independent of the known aldosterone-regulating mechanisms (renin, potassium, adrenocorticotropic hormone), is unrelated to its effect on prolactin and is absent when metoclopramide is directly added to isolated adrenal zona glomerulosa cells. To examine the possibility of a "humoral" mediation of aldosterone stimulation by metoclopramide, we evaluated the effect of serum of 10 normal subjects injected with metoclopramide (10 mg i.v.) on aldosterone production by collagenase-dispersed calf adrenal zona glomerulosa cells. Whereas no effect was observed with serum collected before the injection, serum collected from 5 to 30 min after the injection stimulated aldosterone production. The effect was seen 2.5 min after the injection, was significant at 5 min (P 0.05), 10, 15, 20 and 30 min (P 0.01). The effect disappeared 40 min after the injection, when plasma aldosterone in subjects was still elevated (P 0.01). The biological half-life of the factor (t1/2) is about 12.5 min. A significant correlation was found between the maximal aldosterone response to metoclopramide in vivo and the maximal effect of serum in vitro (r2=0.69;P 0.01). We suggest that metoclopramide stimulates aldosterone production in vivo by the increase in serum of a factor which, in turn, stimulates aldosterone and whose physiological significance remains to be evaluated.