The influence of an uncoupler on amino acid accumulation in Ehrlich mouse ascites tumor cells.
In Ehrlich ascites tumor cells, carbonyl cyanide p-trifluoromethoxyphenylhydrazone (FCCP) acts at two different sites depending upon the concentration employed. (1) In non-glycolysing respiring cells, FCCP is seen to uncouple the mitochondria and thereby it inhibits the ATP-dependent (Na+, K+) pump. (2) In glycolysing cells, FCCP does not affect the electrogenic (Na+, K+) pump, but depolarizes the plasma membrane potential difference as visualized by the distribution of the lipid-soluble cation, tetraphenylphosphonium, and by an inhibition of the rheogenic, Na+-dependent uptake of alpha-aminoisobutyric acid. A depolarization by FCCP also occurs under conditions where a K+-diffusion potential is present and the pump is blocked by metabolic inhibition or by ouabain. Depolarization and FCCP-induced increase in H+ fluxes across the plasma membrane exhibit a similar FCCP-concentration dependency. The imposition of proton-concentration differences in the presence of FCCP inhibits (pHi > pHo) or stimulates (pHi < pHo) alpha-aminoisobutyric acid uptake and tetraphenylphosphonium accumulation. The experiments indicate that FCCP shifts the plasma membrane potential of Ehrlich cells, which are normally relatively impermeable for protons, towards an H+-diffusion potential.
D000596:Amino Acids / Q000378:metabolism*; D000621:Aminoisobutyric Acids / Q000378:metabolism; D000818:Animals; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone / Q000494:pharmacology*; D002286:Carcinoma, Ehrlich Tumor / Q000378:metabolism*; D002463:Cell Membrane Permeability / Q000187:drug effects; D005260:Female; D066298:In Vitro Techniques; D051379:Mice; D008928:Mitochondria / Q000378:metabolism; D009570:Nitriles / Q000494:pharmacology*; D009861:Onium Compounds / Q000378:metabolism; D009943:Organophosphorus Compounds
D000596:Amino Acids; D000621:Aminoisobutyric Acids; D009570:Nitriles; D009861:Onium Compounds; D009943:Organophosphorus Compounds; D002259:Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; C013289:tetraphenylphosphonium