Potentiation of the ACTH Response to Metyrapone by L-Dopa in the Monkey

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Abstract
The i.v. injection of L-dopa (15 mg/kg) to monkeys (Macaca mulatta) failed to alter plasma concentrations of ACTH and of 11-deoxycortisol. When cortisol synthesis was blocked with i.v. metyrapone, potentiation of ACTH secretion by L-dopa became apparent. Simultaneous injection of L-Dopa and metyrapone markedly increased plasma ACTH from 93 .+-. 18 pg/ml to 432 .+-. 80 pg/ml, whereas plasma 11-deoxycortisol increased from 1.5 .+-. 0.2 .mu.g/100 ml to 14.6 .+-. 1.0 .mu.g/100 ml 90 min after treatment. Throughout the experiment the rise in ACTH and in 11-deoxycortisol following coadministration of L-dopa, and metyrapone was significantly (P < 0.01) higher than that produced by metyrapone administration alone. Acute administration of L-dopa in monkeys probably enhances the response of ACTH to metyrapone. L-Dopa (or 1 of its metabolites) probably acts upon a noradrenergic or a dopaminergic system located in the hypothalamus to alter the release of hypothalamic corticotropin regulatory factor(s) and thereby enhance the release of ACTH.

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