Opposite effects of amiloride and amiloride analogues on activation of natural killer cytotoxicity by the phorbol ester TPA and gamma-interferon.
Amiloride, a K(+)-sparing diuretic used as an Na+/H+ exchange inhibitor, blocked the activation of human natural killer (NK) activity against K562 cells by either the phorbol ester TPA or gamma-interferon. However, this stimulation was not blocked by 5-(N,N-hexamethylene)amiloride, a potent inhibitor of Na+/H+ exchange. Spontaneous NK activity was inhibited by this amiloride analogue as well as by 5-(N-methyl-N-guanidinocarbonylmethyl) amiloride, another potent inhibitor of exchange, but only in concentrations 30-80 times higher than those used to inhibit Na+/H+ exchange. The analogue phenamil amiloride blocked NK activity in concentrations found to inhibit epithelial Na+ channels, whereas tetrodotoxin, the specific inhibitor of voltage-dependent Na+ channels, had no effect. These results indicate that Na+/H+ exchange is not essential either for spontaneous NK activity or for its activation by TPA and gamma-interferon. They also suggest the involvement of voltage-independent Na+ channels in NK activity.
Departmento de Bioquímica, ICB, UFRJ, Cidade Universitária, Brazil.
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de Moraes
D000584:Amiloride / Q000031:analogs & derivatives* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D006801:Humans; D007371:Interferon-gamma / Q000494:pharmacology*; D007694:Killer Cells, Natural / Q000187:drug effects*; D015222:Sodium Channels / Q000276:immunology; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D013779:Tetrodotoxin / Q000494:pharmacology
D015222:Sodium Channels; C057360:5-(N,N-hexamethylene)amiloride; D013779:Tetrodotoxin; D000584:Amiloride; D007371:Interferon-gamma; D013755:Tetradecanoylphorbol Acetate