Potentiation of the ACTH response to metyrapone by L-dopa in the monkey.
The intravenous injection of L-Dopa (15 mg/kg) to monkeys (Macaca mulatta) failed to alter plasma concentrations of ACTH and of 11-deoxy-cortisol. When cortisol synthesis was blocked with iv metyrapone, potentiation of ACTH secretion by L-Dopa became apparent. Simultaneous injection of L-Dopa and metyrapone resulted in a marked increase in plasma ACTH from 93 +/- 18 pg/ml to 432 +/- 80 pg/ml, whereas plasma 11-deoxycortisol increased from 1.5 +/- 0.2 mug/100 ml to 14.6 +/- 1.0 mug/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 less than 0.01) higher than that produced by metyrapone administration alone. The results suggest that acute administration of L-Dopa in monkeys enhances the response of ACTH to metyrapone. L-Dopa (or one 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.
D000324:Adrenocorticotropic Hormone / Q000378:metabolism*; D000818:Animals; D003350:Cortodoxone / Q000378:metabolism; D004357:Drug Synergism; D005260:Female; D000882:Haplorhini; D007980:Levodopa / Q000494:pharmacology*; D008253:Macaca mulatta; D008297:Male; D008797:Metyrapone / Q000494:pharmacology*
D007980:Levodopa; D000324:Adrenocorticotropic Hormone; D003350:Cortodoxone; D008797:Metyrapone