Summary There are controversial reports in the literature concerning the effects of opioids on superoxide (O
2
–
) 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 E
1 (PGE
1) with those of various opioids on O
2
–
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 O
2
–
formation in neutrophils with EC
50 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 O
2
–
formation induced by fMet-Leu-Phe. ATP at a concentration of 100 M and the opioids, methionine enkephalin, -endorphin, dynorphin, [
d-Ala
2, N-Me-Phe
4, Gly
5-ol]-enkephalin, [
d-Ala
2-
d-Leu
5]-enkephalin and morphine at concentrations between 10 pM to 1 M did not activate O
2
–
formation. ATP but not \-endorphin potentiated fMet-Leu-Phe-induced O
2
–
formation. O
2
–
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 PGE
1. 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. PGE
1 strongly inhibited fMet-Leu-Phe-induced O
2
–
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 O
2
–
formation. Our results show that O
2
–
formation is differentially regulated by various classes of intercellular signal molecules and that opioids do not play a role in the regulation of O
2
–
formation. The precise definition of the experimental conditions and control experiments with established modulators of O
2
–
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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