Effects of myristate phorbol ester on V-ATPase activity and Na(+)-H+ exchange in alveolar macrophages.
The roles of protein kinase C (PKC) in regulation of the plasmalemmal vacuolar-type H(+)-ATPase (V-ATPase) and Na(+)-H+ exchanger (NHE) of rabbit alveolar macrophages (m phi) were investigated using phorbol 12-myristate 13-acetate (PMA). At an extracellular pH (pHo) of 7.4 (nominal absence of CO2-HCO3-), PMA caused a dose-dependent increase in the rate of cellular H+ extrusion with little change in intracellular pH (pHi). PMA caused a prolonged cytosolic acidification at pHo < or = 6.8. PMA-induced changes in pHi were sensitive to bafilomycin A1, but were insensitive to amiloride. Studies of pHi recovery following intracellular acid challenge showed that both V-ATPase and the NHE were up-regulated by PMA. An inactive analog, 4 alpha-phorbol, had no detectable effects on pHi homeostasis. These data indicate that (a) PKC is involved in regulation of V-ATPase and the NHE of resident alveolar m phi and (b) V-ATPase is the predominant mechanism for pHi homeostasis in unstimulated and PMA-activated m phi.
Heming
T A
TA
Department of Internal Medicine, University of Texas Medical Branch, Galveston 77555-0876, USA.
Bidani
A
A
D000255:Adenosine Triphosphate / Q000378:metabolism; D000584:Amiloride / Q000494:pharmacology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D004789:Enzyme Activation; D006706:Homeostasis; D006863:Hydrogen-Ion Concentration; D018942:Macrolides; D016676:Macrophages, Alveolar / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism*; D011493:Protein Kinase C / Q000378:metabolism / Q000502:physiology; D006180:Proton-Translocating ATPases / Q000187:drug effects* / Q000378:metabolism*; D011817:Rabbits; D012964:Sodium / Q000378:metabolism / Q000494:pharmacology; D017923:Sodium-Hydrogen Exchangers / Q000187:drug effects* / Q000378:metabolism*; D013755:Tetradecanoylphorbol Acetate / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology; D014617:Vacuoles / Q000201:enzymology
D000900:Anti-Bacterial Agents; D018942:Macrolides; D017923:Sodium-Hydrogen Exchangers; C057620:bafilomycin A; D000584:Amiloride; D000255:Adenosine Triphosphate; D012964:Sodium; D011493:Protein Kinase C; D006180:Proton-Translocating ATPases; D013755:Tetradecanoylphorbol Acetate