Effect of metergoline on the aldosterone-stimulating properties of metoclopramide

The mechanism by which metoclopramide stimulates aldosterone secretion is still unclear, since it cannot be explained by known regulatory systems. On the other hand we have recently shown that serotonin is also a potent aldosterone-stimulatory substance in man and its action can be blunted by the antiserotoninergic drug, metergoline. To test if metoclopramide could act through a serotoninergic pathway we have studied the effect of metergoline on the aldosterone response to metoclopramide in 8 normal subjects. The effect of metoclopramide (10 mg i.v.) on plasma aldosterone, PRA, cortisol, prolactin and K was studied before and after acute metergoline administration. Metergoline pretreatment significantly reduced the aldosterone response to metoclopramide, together with a slight reduction of prolactin, whereas no changes were seen on PRA, cortisol and K. In vitro, metoclopramide induced a significant aldosterone output from human adrenal adenoma cells, which was partially reduced by metergoline and not by bromocriptine. Despite a lack of specificity of metergoline these data may suggest the hypothesis of a serotoninergic component in the aldosterone-stimulating properties of metoclopramide.