AJP - Endocrinology and Metabolism, Vol 243, Issue 5 375-E379, Copyright © 1982 by American Physiological Society
Modulation of corticosteroid secretion by dopaminergic mechanisms in rhesus monkeys
J. R. Sowers
This study was designed to investigate dopaminergic mechanisms in the
control of corticosteroid secretion. Ten rhesus monkeys received
metoclopramide (1.25 mg iv) or domperidone (1.25 mg iv) with 5% dextrose
(vehicle) or with dopamine (4 micrograms.kg-1.min-1) infusions begun 60 min
before administration of the dopamine antagonist. Metoclopramide, in the
presence of vehicle, increased plasma 18-hydroxycorticosterone from 11.2
+/- 1.0 ng/dl to a maximum concentration of 50 +/- 5.1, plasma aldosterone
from 5.4 +/- 0.7 ng/dl to a maximum of 38.2 +/- 4.9, and prolactin (PRL)
concentrations from 8.5 +/- 1.2 ng/ml to a maximum of 114.6 +/- 7.2.
Domperidone, in the presence of vehicle, increased plasma PRL
concentrations from 8.6 +/- 1.2 ng/ml to a maximum of 148.7 +/- 7.8 but had
no effect on plasma corticosteroids. Dopamine infusion inhibited the
18-hydroxycorticosterone, aldosterone, and PRL response to metoclopramide
and the PRL response to domperidone. These results demonstrate that
18-hydroxycorticosterone and aldosterone responses to metoclopramide and
PRL responses to metoclopramide and domperidone are mediated by their
antagonist activity at dopamine receptors. Domperidone may fail to
stimulate aldosterone secretion because it does not cross the blood-brain
barrier or fails to act as an antagonist at the glomerulosa dopamine
receptor through which dopaminergic modulation of corticosteroid secretion
is mediated. A parallel time course of stimulation of
18-hydroxycorticosterone and aldosterone secretion without changes in other
aldosterone precursors suggests that dopamine modulates the activity of the
glomerulosa 18-hydroxylase enzyme.
