Modulation of corticosteroid secretion by dopaminergic mechanisms in rhesus monkeys.
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.
D015069:18-Hydroxycorticosterone / Q000097:blood; D000305:Adrenal Cortex Hormones / Q000378:metabolism*; D000450:Aldosterone / Q000097:blood; D000818:Animals; D004294:Domperidone / Q000494:pharmacology*; D004298:Dopamine / Q000494:pharmacology*; D007700:Kinetics; D008253:Macaca mulatta; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology*; D011388:Prolactin / Q000097:blood
D000305:Adrenal Cortex Hormones; D000450:Aldosterone; D004294:Domperidone; D015069:18-Hydroxycorticosterone; D011388:Prolactin; D008787:Metoclopramide; D004298:Dopamine