Metoclopramide Inhibits Aldosterone Biosynthesis in Vitro

Metoclopramide, a dopaminergic antagonist, has consistently elevated plasma aldosterone levels in vivo. To determine whether this was a direct action of metoclopramide on adrenal steroidogenesis, we examined the response of collagenase- dispersed rat adrenal glomerulosa cells to metoclopramide in vitro. The effect of increasing concentrations of metoclopramide (3 × 10-10 to 3 × 10-4 M) on basal as well as angiotensin II (2.4 × HT10-10 to 2.4 × 10-8 M)-, ACTH (3.5 × 10-11 M)- and potassium (5.9 meq/liter) -stimulated aldosterone production was evaluated. Metoclopramide caused a dose-related decrease in basal and stimulated aldosterone production (P < 0.01). In addition, metoclopramide also blocked basal and stimulated corticosterone production (P < 0.01). This was not due to an irreversible toxic effect, since glomerulosa cells preincubated with 3 × 10-4 M metoclopramide excluded trypan blue dye and responded to ACTH stimulation. Sodium metabisulfite, an antioxidant present in the metoclopramide preparatio...