Phorbol 12-myristate 13-acetate activates an electrogenic H(+)-conducting pathway in the membrane of neutrophils.
The mode of activation of an H(+)-conducting pathway present in the membrane of neutrophils was investigated. (1) Resting neutrophils released protons through an electrogenic Cd(2+)-inhibitable (K0.5 approximately 20 microM) route when a pH gradient and appropriate charge compensation was provided. (2) The rate of H+ efflux was stimulated over 2.5-fold by 4 beta-phorbol 12-myristate 13-acetate (PMA; K0.5 approximately 0.7 nM) or by 4 beta-phorbol 12,13-dibutyrate (K0.5 approximately 20 nM) even when the NADPH oxidase was blocked by p-chloromercuribenzoate. (3) Staurosporine inhibited the effect of PMA. (4) The H+ egress was not enhanced by 4 alpha-phorbol 12,13-didecanoate. (5) Low concentrations of Cd2+ (less than 40 microM) inhibited the H+ flux without influencing the oxidase. The results raise the possibility that protein kinase C could be involved in the activation of an electrogenic H(+)-conducting pathway in the membrane of neutrophils. The activation of this route by phorbol esters seems to be independent of the stimulation of NADPH oxidase.
Kapus
A
A
Department of Physiology, Semmelweis University Medical School, Budapest, Hungary.
Szászi
K
K
Ligeti
E
E
D000818:Animals; D001692:Biological Transport; D002104:Cadmium / Q000494:pharmacology; D002462:Cell Membrane / Q000187:drug effects / Q000502:physiology*; D002463:Cell Membrane Permeability; D002729:Chloromercuribenzoates / Q000494:pharmacology; D006863:Hydrogen-Ion Concentration; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors / Q000378:metabolism; D019255:NADPH Oxidases; D009504:Neutrophils / Q000187:drug effects / Q000502:physiology*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000378:metabolism; D011522:Protons; D013552:Swine; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D014634:Valinomycin / Q000494:pharmacology; D020245:p-Chloromercuribenzoic Acid
D002729:Chloromercuribenzoates; D007473:Ion Channels; D011522:Protons; D002104:Cadmium; D014634:Valinomycin; D015240:Phorbol 12,13-Dibutyrate; D020245:p-Chloromercuribenzoic Acid; D009247:NADH, NADPH Oxidoreductases; D019255:NADPH Oxidases; D011493:Protein Kinase C; D013755:Tetradecanoylphorbol Acetate