Evidences for a dopamine-regulated peripheral source of circulating beta-endorphin

Area of Science:

• Neuroendocrinology
• Pharmacology
• Hormone Regulation

Background:

• Circulating beta-endorphin (beta EP) and beta-lipotropin (beta LPH) levels rise with acetylcholine or serotonin agonists.
• The role of dopamine in regulating these proopiomelanocortin (POMC) peptides is not fully understood.

Purpose of the Study:

• To investigate the effects of dopamine receptor agonists and antagonists on plasma beta EP, beta LPH, cortisol, and prolactin (PRL) in healthy subjects.
• To explore the potential source and regulation of circulating beta EP.

Main Methods:

• Administration of various dopamine agonists (DA, bromocriptine, L-dopa, nomifensine) and antagonists (metoclopramide, domperidone) to normal subjects.
• Measurement of plasma beta EP, beta LPH, cortisol, and PRL levels before and after drug administration.
• Investigated effects of L-dopa, DA infusion, and dexamethasone pretreatment on antagonist-induced peptide level changes.

Main Results:

• Dopamine agonists did not significantly alter plasma beta EP or beta LPH levels.
• Metoclopramide (dopamine antagonist) significantly increased beta EP, beta LPH, PRL, and cortisol.
• Domperidone (peripheral dopamine antagonist) increased only beta EP, an effect not altered by dexamethasone, suggesting a non-pituitary source.

Conclusions:

• Endogenous dopamine appears to inhibit the secretion of POMC-related peptides.
• A corticotropin-releasing hormone-independent source of circulating beta EP exists in humans, regulated by dopamine.