Lauer C G, Braley L M, Menachery A I, Williams G H
Endocrinology. 1982 Jul;111(1):238-43. doi: 10.1210/endo-111-1-238.
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.
甲氧氯普胺是一种多巴胺能拮抗剂，在体内可使血浆醛固酮水平持续升高。为了确定这是否是甲氧氯普胺对肾上腺类固醇生成的直接作用，我们在体外研究了胶原酶分散的大鼠肾上腺球状带细胞对甲氧氯普胺的反应。评估了甲氧氯普胺浓度增加（3×10⁻¹⁰至3×10⁻⁴M）对基础以及血管紧张素II（2.4×10⁻¹⁰至2.4×10⁻⁸M）、促肾上腺皮质激素（3.5×10⁻¹¹M）和钾（5.9毫当量/升）刺激的醛固酮生成的影响。甲氧氯普胺导致基础和刺激的醛固酮生成呈剂量相关的下降（P＜0.01）。此外，甲氧氯普胺还阻断基础和刺激的皮质酮生成（P＜0.01）。这并非由于不可逆的毒性作用，因为用3×10⁻⁴M甲氧氯普胺预孵育的球状带细胞可排斥台盼蓝染料并对促肾上腺皮质激素刺激有反应。偏亚硫酸氢钠是甲氧氯普胺制剂中的一种抗氧化剂，它对甲氧氯普胺的作用无影响。这些结果表明，与体内获得的报道数据相反，甲氧氯普胺在体外是一种醛固酮拮抗剂。因此，甲氧氯普胺可能是一种部分多巴胺能激动剂：在体外多巴胺水平可忽略不计的情况下，它是一种激动剂，而在体内多巴胺浓度较高的情况下，它是一种拮抗剂。
