Beta-endorphin and related peptides suppress phorbol myristate acetate-induced respiratory burst in human polymorphonuclear leukocytes.
In the present study, the immunomodulatory effect of beta-endorphin (beta-E) and shorter pro-opiomelanocortin (POMC) fragments was evaluated by assessing their influence on respiratory burst in human polymorphonuclear leukocytes (PMN). The effect of the peptides (10(-17)M - 10(-10)M) on phorbol myristate acetate (PMA)-stimulated production of reactive oxygen metabolites was measured in a lucigenin-enhanced chemiluminescence (CL) assay. Both POMC peptides with opiate-like activity (i.e. alpha-endorphin (alpha-E), beta-E and gamma-endorphin (gamma-E] and their non-opioid derivatives (i.e. des-TYR1-beta-endorphin (dT beta E), des-TYR1-gamma-endorphin (dT gamma E), and des-ENK-gamma-endorphin (dE gamma E] were tested. With the exception of alpha-E, PMA-stimulated respiratory burst was suppressed by all POMC fragments tested. A U-shaped dose-response relation was observed. Doses lower than 10(-17)M and higher than 10(-8)M were without effect. beta-E and dT beta E both suppressed PMA-induced oxidative burst in human PMN at physiological concentrations (10(-16)M - 10(-10)M). gamma-E and dT gamma E proved to be less potent inhibitors, reaching maximal effect at higher concentrations (10(-12)M - 10(-10)M). DE gamma E exerted an even less pronounced but still significant suppressive effect at the concentration of 10(-10)M. None of the endorphins tested was shown to affect resting oxidative metabolism in the PMN. The modulatory effects of the opioid peptides could not be blocked by the opioid antagonist naloxone (10(-8)M). These data show that fragments derived from the POMC-precursor molecule modulate the activation of PMN by suppressing PMA-stimulated oxidative metabolism and that this activity does not involve a classical opiate-like receptor.
Diamant
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M
Rudolf Magnus Institute, Medical Faculty, University of Utrecht, The Netherlands.
Henricks
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PA
Nijkamp
F P
FP
de Wied
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D004723:Endorphins / Q000494:pharmacology*; D006801:Humans; D066298:In Vitro Techniques; D007700:Kinetics; D008163:Luminescent Measurements; D009270:Naloxone / Q000494:pharmacology; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects*; D011333:Pro-Opiomelanocortin / Q000494:pharmacology; D013329:Structure-Activity Relationship; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D001615:beta-Endorphin / Q000494:pharmacology*
D004723:Endorphins; D009270:Naloxone; D001615:beta-Endorphin; D011333:Pro-Opiomelanocortin; D013755:Tetradecanoylphorbol Acetate