Specificity of metoclopramide in assessing the role of dopamine in regulating aldosterone secretion.

Abstract

To evaluate the specificity of metoclopramide as a dopamine antagonist on the rat glomerulosa cell, the effects of dopamine (1 × 10-10 to 1 × 10-6 M), metoclopramide (1 × 10-10 and 1 × 10-7 M), and serotonin (1 × 10-8 and 1 × 10-6 M), alone and in combination, on basal and/r angiotensin II (AII)-stimulated aldosterone secretion was assessed. While neither dopamine nor metoclopramide altered basal aldosterone production in these cells, both caused a dose-related inhibition of AII-stimulated steroidogenesis (P < 0.01). Both produced their maximal inhibitory effect at a concentration of 10-7 M, with a reduction in aldosterone output from 221 ± 28 ng/106 cells with AII alone to 146 ± 27 and 141 ± 28 ng/106 cells with dopamine and metoclopramide, respectively. When metoclopramide was added to incubates containing 10-6 M dopamine and 2.4 × 10-9 M AII, aldosterone production was significantly increased from 141 ± 22 ng/106 to 220 ± 46 ng/106 cells, an output indistinguishable from that produced by AII alone. In ...