Evidences for a dopamine-regulated peripheral source of circulating beta-endorphin.
Circulating beta-endorphin (beta EP) and beta-lipotropin (beta LPH) concentrations increase after the administration of acetylcholine or serotonin agonist drugs. In this study we examined the effect of dopamine receptor agonists and/or antagonists on plasma beta EP, beta LPH, cortisol, and PRL levels in normal subjects. Neither direct dopamine (DA) agonist drugs, DA (1 microgram/kg min for 120 min), bromocriptine (2.5 mg po), L-dopa (500 mg po) or an indirect DA agonist, nomifensine (200 mg po), significantly altered plasma beta EP and beta LPH levels. The administration of metoclopramide, a DA antagonist (10 mg iv), significantly increased plasma beta EP, beta LPH, PRL, and cortisol levels. This effect was completely reversed by pretreatment with L-dopa (500 mg po) and only partially antagonized by DA infusion. Domperidone (10 mg iv), a DA antagonist which does not cross the blood brain barrier, increased only plasma beta EP levels, an effect inhibited both by L-dopa and DA. After dexamethasone (2 mg/day for 2 days) domperidone still increased plasma beta EP and PRL levels. The concomitant increase of beta EP, beta LPH, and cortisol after metoclopramide suggests that endogenous DA inhibits the secretion of proopiomelanocortin-related peptides. Moreover, since domperidone increases only beta EP and this effect is not altered by dexamethasone, there may be a corticotropin-releasing hormone-independent source of circulating beta EP in humans, which is inhibited by DA.
D000109:Acetylcholine / Q000494:pharmacology; D000328:Adult; D001812:Blood-Brain Barrier; D001971:Bromocriptine / Q000494:pharmacology; D003907:Dexamethasone / Q000494:pharmacology; D004294:Domperidone / Q000494:pharmacology; D004298:Dopamine / Q000502:physiology*; D006801:Humans; D007980:Levodopa / Q000494:pharmacology; D008297:Male; D008787:Metoclopramide / Q000494:pharmacology; D009627:Nomifensine / Q000494:pharmacology; D012016:Reference Values; D001615:beta-Endorphin / Q000097:blood*; D008083:beta-Lipotropin / Q000097:blood
D009627:Nomifensine; D001971:Bromocriptine; D007980:Levodopa; D004294:Domperidone; D001615:beta-Endorphin; D003907:Dexamethasone; D008083:beta-Lipotropin; D008787:Metoclopramide; D000109:Acetylcholine; D004298:Dopamine