Lack of effect of opioid peptides, morphine and naloxone on superoxide formation in human neutrophils and HL-60 leukemic cells.
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 microM and the opioids, methionine enkephalin, beta-endorphin, dynorphin, [D-Ala2, N-Me-Phe4, Gly5-ol]-enkephalin, [D-Ala2-D-Leu5]-enkephalin and morphine at concentrations between 10 pM to 1 microM did not activate O2- formation. ATP but not beta-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 beta-endorphin. PGE1 strongly inhibited fMet-Leu-Phe-induced O2- formation, whereas morphine, methionine enkephalin and the opioid antagonist, naloxone, were without effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Seifert
R
R
Institut für Pharmakologie, Freie Universität Berlin.
Burde
R
R
Schultz
G
G
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000527:Alprostadil / Q000494:pharmacology; D001711:Biotransformation / Q000187:drug effects; D004723:Endorphins / Q000494:pharmacology*; D004744:Enkephalin, Methionine / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D007942:Leukemia, Experimental / Q000378:metabolism; D009020:Morphine / Q000494:pharmacology*; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000494:pharmacology; D009270:Naloxone / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects / Q000378:metabolism*; D010101:Oxygen Consumption / Q000187:drug effects; D010972:Platelet Activating Factor / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism*; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D004723:Endorphins; D010972:Platelet Activating Factor; D013481:Superoxides; D009270:Naloxone; D004744:Enkephalin, Methionine; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009020:Morphine; D000255:Adenosine Triphosphate; D000527:Alprostadil