Mechanisms for the uptake of cationic drugs by the liver: a study with tributylmethylammonium (TBuMA).

摘要: The mechanisms of hepatic organic cation transport were examined in isolated rat hepatocytes, using the model compound [methyl-3H]tributylmethylammonium (TBuMA). [3H]TBuMA is shown to be taken up into hepatocytes by two carrier-mediated systems addition a nonsaturable process. for TBuMA share common features with both type I and II carrier reported exogenous cations such as procainamide ethobromide vecuronium, respectively. Only slight effects seen presence relatively high concentrations endogenous thiamine, choline N1-methyl nicotinamide. total uptake was neither influenced an electronegative membrane potential variations external internal pH, nor absence Na+, K+ or Cl- incubation medium. inorganic anion I- stimulated [3H]TBuMA. An improved presentation binding may involved because symport could not demonstrated. Lowering temperature produced significant reduction velocity [3H] TBuMA, whereas metabolic inhibitors valinomycin carbonylcyanide-m-chlorphenylhydrazone reduced rate 80 90%, respectively, which correlated extent ATP depletion. It concluded that monovalent cationic drug can considered mixed I/type exhibits electroneutral anion-sensitive mechanism, depending on energy. mechanism dissimilar from Na(+)-dependent H(+)-dependent have been described cations, N1-methylnicotinamide.