Lack of effect of opioid peptides,morphine and naloxone on superoxide formation in human neutrophils and HL-60 leukemic cells |
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Authors: | Roland Seifert Rahel Burde Günter Schultz |
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Affiliation: | (1) Institut für Pharmakologie, Freie Universität Berlin, Thielallee 69/73, D-1000, 33 Berlin |
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Abstract: | Summary There are controversial reports in the literature concerning the effects of opioids on superoxide (O2–) formation in phagocytes, these agents being either inhibitory or stimulatory. We re-examined this issue and compared the effects of the Chemotactic peptide, N-formyl-l,-methionyl-l-leucyl-l-phenylalanine (fMet-Leu-Phe), phorbol myristate acetate (PMA), ATP, platelet activating factor (PAF), cytochalasin B (CB) and prostaglandin E1 (PGE1) with those of various opioids on O2–formation in human neutrophils and HL-60 leukemic cells under defined experimental conditions. In the presence of CB, fMet-Leu-Phe and PAF concentration-dependently activated O2–formation in neutrophils with EC50 values of 20 nM and 100 nM, respectively. In the absence of CB, fMet-Leu-Phe and PAF were much less effective. PAF synergistically enhanced O2–formation induced by fMet-Leu-Phe. ATP at a concentration of 100 M and the opioids, methionine enkephalin, -endorphin, dynorphin, [d-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin, [d-Ala2-d-Leu5]-enkephalin and morphine at concentrations between 10 pM to 1 M did not activate O2–formation. ATP but not -endorphin potentiated fMet-Leu-Phe-induced O2–formation. O2–formation induced by a maximally stimulatory concentration of PMA (100 ng/ml) was enhanced by fMet-Leu-Phe but was unaffected by methionine enkephalin or PGE1. PMA at a non-stimulatory concentration (2 ng/ml) potentiated the effect of fMet-Leu-Phe but did not induce responsiveness to PAF, ATP or -endorphin. PGE1 strongly inhibited fMet-Leu-Phe-induced O2–formation, whereas morphine, methionine enkephalin and the opioid antagonist, naloxone, were without effect. In HL-60 cells differentiated with dibutyryl cAMP, fMet-Leu-Phe, PAF and ATP but not -endorphin activated O2–formation. Our results show that O2–formation is differentially regulated by various classes of intercellular signal molecules and that opioids do not play a role in the regulation of O2–formation. The precise definition of the experimental conditions and control experiments with established modulators of O2–formation are essential to evaluate the role of opioids in the regulation of this effector system.Send offprint requests to R. Seifert at the above address |
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Keywords: | NADPH oxidase Chemotactic peptides Receptor synergism Opioids Phorbol myristate acetate |
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