Adrenocorticotropin-Mediated Effect of Metoclopramide on Plasma Aldosterone in Man*

Abstract

Five healthy adult men were given metoclopramide (10 and 20 mg) iv and the effects of L-dopa and dexamethasone on metoclopramide-induced increases in plasma aldosterone concentration were determined. Plasma PRL, ACTH, and cortisol levels were also measured and the results reported in a previous study. After an injection of 10 mg metoclopramide, aldosterone levels increased significantly. The aldosterone rise was inhibited by L-dopa, but not by dexamethasone. After injecting 20 mg metoclopramide, aldosterone levels increased significantly vs. both the control and the basal level. The aldosterone increase was not inhibited by L-dopa pretreatment, whereas pretreatment with dexamethasone did suppress it. The data suggest that metoclopramide increased aldosterone secretion through an ACTH-dependent (stress mediated) effect in addition to its antidopaminergic adrenal action, simultaneously. There were no significant differences between the ACTH-dependent and dopamine antagonist-mediated aldosterone increases in either the 10- or 20-mg tests. However, the ACTH-dependent aldosterone increase was statistically greater in the 20-mg test than in the 10-mg test, whereas there was only a slight and not statistically significant difference in the dopamine antagonist-mediated aldosterone increase between the tests. This means that the ACTH-dependent component of the aldosterone secretion is affected by the doubling of the metoclopramide dose, whereas the dopamine antagonist-mediated component is not.

Endogenous Dopaminergic Inhibition of Aldosterone and Prolactin Secretion is Apparently not Increased in Primary Aldosteronism

“…In healthy subjects in whom dopaminergic activity was increased by exogenous dopamine or dopamine agonist pretreatment the dose-response relation of hormone stimulation by metoclopramide was found shifted to the right together with a relative hyperresponse to high-dose metoclopramide (Kitaoka, Takebe, Kobayashi, Nakazono and Kudo 1980);Nishida, Matsuki, Nagase, Horino, Endoh, Kakita, Tenku and Oyama 1983). Therefore, the findings in our patients with primary aldosteronism are not consistent with the suggestion oiKuchel et al 1980, of an increased endogenous dopaminergic inhibition of aldosterone and prolactin secretion in this disorder.…”

Atrial natriuretic factor inhibits metoclopramide stimulated aldosterone release in man.

“…However, when the normal diurnal variation in cortisol was taken into account, a rise in cortisol at 40 min was observed after administration of metoclopramide (Nishida et al, 1983a). The mechanism of this rise in cortisol remains unclear although it could perhaps be due to metoclopramide causing stress and hence ACTH secretion (Nishida et al, 1983b). This could have been true in the present study since the volunteers almost always developed transient restlessness (without any detectable increase in extrapyramidal activity) lasting 10-30 min after administration of metoclopramide which was accompanied by a rise in both heart rate and blood pressure.…”

Dopaminergic binding and inhibitory effect in the bovine adrenal zona glomerulosa.

“…A similar dexamethasone-induced attenuation of the aldosterone response to higher doses of metoclopramide has been also demonstrated in humans. 21 If dopamine inhibits the secretion of aldosterone at the adrenal level, its action might be exerted through local dopaminergic receptors. Preliminary evidence suggests that rat 22 and calf 23 adrenal zona glomerulosa (AZG) contain dopamine binding sites.…”