Differential effects of metabolic inhibitors on cellular and mitochondrial uptake of organic cations in rat liver

Biochemical Pharmacology
H SteenD K Meijer

Abstract

The effects of several metabolic inhibitors on the uptake of tri-n-butylmethylammonium (TBuMA) were studied in isolated rat liver mitochondria, isolated rat hepatocytes and isolated perfused rat livers, in order to characterize further the mechanisms for carrier-mediated uptake and cellular accumulation of organic cations in the liver. Treatment of isolated hepatocytes with valinomycin, carbonylcyanide-m-chlorophenyl-hydrazone (CCCP), dinitrophenol, oligomycin or antimycin resulted in a rapid decrease in cellular ATP within 3 min of addition. The initial uptake rate of TBuMA was generally largely affected by these treatments. However, fructose at 10 mM had no effect at all on the uptake rate of the cation whereas cellular ATP was decreased to an extent comparable to that after treatment with the metabolic inhibitors. Consequently it was hypothesized that the metabolic inhibitors affected the initial cellular uptake rate of organic cations due to either altered intracellular sequestration (e.g. mitochondria) or alternatively to direct effects on the plasma membrane rather than by decreasing cellular ATP. Isolated rat mitochondria were shown to take up organic cations very efficiently. Accumulation in this organelle is probably d...Continue Reading

References

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Citations

Jan 27, 1999·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·J H HayesJ L Boyer
Jul 17, 1995·Biochimica Et Biophysica Acta·R P Oude ElferinkG M Groothuis
Mar 4, 2000·Advanced Drug Delivery Reviews·M P Murphy, R A Smith
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Feb 5, 2015·BioMed Research International·Victor JegerSiamak Djafarzadeh
May 12, 2016·Chemical Communications : Chem Comm·Shubhanchi NigamStephen J Archibald
Nov 1, 1993·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·H SteenD K Meijer
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Apr 16, 1998·Hepatology : Official Journal of the American Association for the Study of Liver Diseases·J W SmitD K Meijer
Mar 26, 2021·Spectrochimica Acta. Part A, Molecular and Biomolecular Spectroscopy·Dingyi GuoWeiying Lin
Oct 6, 2012·Journal of Nuclear Medicine : Official Publication, Society of Nuclear Medicine·Dong-Yeon KimJung-Joon Min

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