Inhibition of human natural killer (NK) activity by calcium channel modulators and a calmodulin antagonist.
The presence of calcium (Ca2+) in the culture medium is a requirement for the NK cytotoxic reaction. To further explore the role of Ca2+ and calmodulin (a cytoplasmic protein that mediates most of the biological effects of Ca2+) in this process, we evaluated the effects of nifedipine (a Ca2+ channel antagonist), BAY-K-8644 (a Ca2+ channel agonist), and haloperidol (an inhibitor of calmodulin) on the NK activity of human peripheral blood mononuclear cells (PBMC), and the augmentation of this activity by recombinant interleukin 2 (r-IL 2) and interferon-gamma (r-gamma-IFN). We found that all of these drugs inhibit NK activity in a dose-dependent fashion. This appears to result from interference with the programming for lysis stage of the lytic process. In contrast, the presence of these agents during the incubation of PBMC with r-IL 2 or r-gamma-IFN did not induce any change in the enhancement of NK activity. These data suggest that Ca2+ exerts its effect at the intracellular level during the NK cytotoxic process, and that the augmentation of NK activity by lymphokines is independent of the calcium-calmodulin system.
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D002118:Calcium / Q000502:physiology*; D002147:Calmodulin / Q000037:antagonists & inhibitors; D003602:Cytotoxicity, Immunologic / Q000187:drug effects*; D003864:Depression, Chemical; D004347:Drug Interactions; D005089:Exocytosis / Q000187:drug effects; D006220:Haloperidol / Q000494:pharmacology*; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology; D007376:Interleukin-2 / Q000494:pharmacology; D007473:Ion Channels / Q000187:drug effects* / Q000502:physiology; D007694:Killer Cells, Natural / Q000187:drug effects* / Q000276:immunology; D009543:Nifedipine / Q000494:pharmacology*; D011994:Recombinant Proteins / Q000494:pharmacology
D002147:Calmodulin; D007376:Interleukin-2; D007473:Ion Channels; D011994:Recombinant Proteins; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D007371:Interferon-gamma; D009543:Nifedipine; D006220:Haloperidol; D002118:Calcium