title: Inhibition by naloxone of neutrophil superoxide release: a potentially useful antiinflammatory effect.
abstract: The working hypothesis of many studies of shock has been that naloxone acts by blocking centrally and/or peripherally located opioid receptors. At plasma concentrations used to treat experimental shock (10(-6) M and above), naloxone inhibited the in vitro release of superoxide (O2-) by human neutrophils that were stimulated by the E. coli peptide N-formyl methionyl leucyl phenylalanine (FMLP). Superoxide release stimulated by phorbol 12,13-dibutyrate (PDB) was also inhibited by naloxone. Naloxone had no effect on the FMLP-stimulated release of beta-glucuronidase or lysozyme. Naloxone had no effect on 3H FMLP receptor binding. Studies utilizing 3H naloxone revealed the presence of a ligand-specific naloxone binding site on human neutrophils with a Kd of 1.2 X 10(-5) M, which is close to the ID50 of the inhibitory effect upon O2- release (1.8 X 10(-5). Thyrotropin releasing factor (TRF) had no effect upon 3H naloxone binding or on O2- release. Verapamil, a calcium channel blocker, inhibited 3H naloxone binding, and O2- release while nifedipine, another calcium channel blocker had no effect on either assay except at 10(-4) M, at which concentration 3H naloxone binding as well as the release of O2- were increased. These experiments suggest that the inhibitory effect of naloxone upon O2- release is mediated via a specific binding site.
mesh_terms: D001667:Binding, Competitive; D002118:Calcium / Q000378:metabolism; D006801:Humans; D066298:In Vitro Techniques; D009240:N-Formylmethionine Leucyl-Phenylalanine / Q000037:antagonists & inhibitors; D009270:Naloxone / Q000097:blood / Q000494:pharmacology*; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D015240:Phorbol 12,13-Dibutyrate; D010703:Phorbol Esters / Q000037:antagonists & inhibitors; D011957:Receptors, Opioid / Q000378:metabolism; D013481:Superoxides / Q000097:blood*; D014700:Verapamil / Q000378:metabolism / Q000494:pharmacology
chemical_list: D010703:Phorbol Esters; D011957:Receptors, Opioid; C034565:naloxone receptor; D013481:Superoxides; D009270:Naloxone; D015240:Phorbol 12,13-Dibutyrate; D009240:N-Formylmethionine Leucyl-Phenylalanine; D014700:Verapamil; D002118:Calcium