Endocrinology, Vol 111, 238-243, Copyright © 1982 by Endocrine Society
Metoclopramide inhibits aldosterone biosynthesis in vitro
CG Lauer, LM Braley, AI Menachery and GH Williams
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 X
10(-10) to 3 X 10(-4) M) on basal as well as angiotensin II (2.4 X 10(-10)
to 2.4 X 10(-8) M)-, ACTH (3.5 X 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 less than 0.01). In addition, metoclopramide also blocked
basal and stimulated corticosterone production (P less than 0.01). This was
not due to an irreversible toxic effect, since glomerulosa cells
preincubated with 3 X 10(-4) M metoclopramide excluded trypan blue dye and
responded to ACTH stimulation. Sodium metabisulfite, an antioxidant present
in the metoclopramide preparation, did not contribute to the metoclopramide
effect. These results indicate that metoclopramide is an aldosterone
antagonist in vitro, contrary to reported data obtained in vivo. Thus,
metoclopramide may be a partial dopaminergic agonist: in vitro where
dopamine levels are negligible, it is an agonist, whereas in vivo where
dopamine concentrations are greater, it is an antagonist.
