Effects of trifluoperazine on human neutrophil function.
The interaction of cytochalasin B-treated human neutrophils with the synthetic tripeptide, N-formyl-methionyl-leucyl-phenylalanine (FMLP) results in a time- and concentration-dependent generation of superoxide anion (O2-) by an extracellular release of granule-associated beta-glucuronidase and lysozyme from these cells. Granule exocytosis was not accompanied by significant cytoplasmic lactate dehydrogenase extrusion. FMLP-stimulated O2- production occurs but is significantly curtailed in the absence of extracellular calcium. Nevertheless, incubation of neutrophils with EGTA in calcium-free medium had no effect on the O2- -generating system. Trifluoperazine (TFP), an inhibitor of calmodulin (a calcium-binding protein), caused a dose-related inhibition of FMLP-elicited degranulation and O2- production in the presence of absence of extracellular calcium. This effect TFP could be reversed by washing the cells before contact with FMLP. These data suggest that TFP represents a useful tool for defining the relevance of calmodulin and calcium to neutrophil function.
D002478:Cells, Cultured; D003571:Cytochalasin B / Q000494:pharmacology; D003594:Cytoplasmic Granules / Q000187:drug effects / Q000201:enzymology; D004305:Dose-Response Relationship, Drug; D005089:Exocytosis / Q000187:drug effects; D006801:Humans; D009239:N-Formylmethionine / Q000031:analogs & derivatives / Q000494:pharmacology; D009240:N-Formylmethionine Leucyl-Phenylalanine; D009504:Neutrophils / Q000187:drug effects* / Q000378:metabolism; D009842:Oligopeptides / Q000494:pharmacology; D013481:Superoxides / Q000378:metabolism; D014268:Trifluoperazine / Q000494:pharmacology*
D009842:Oligopeptides; D013481:Superoxides; D014268:Trifluoperazine; D003571:Cytochalasin B; D009239:N-Formylmethionine; D009240:N-Formylmethionine Leucyl-Phenylalanine