Effect of ethanol on hepatobiliary transport of cationic drugs. A study in the isolated perfused rat liver, rat hepatocytes and rat mitochondria
Autor: | Herman Steen, Dirk K. F. Meijer, Marjolijn T. Merema |
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Rok vydání: | 1994 |
Předmět: |
Male
Mitochondria Liver Acetaldehyde Procainamide Ouabain chemistry.chemical_compound medicine Animals Choline Rats Wistar Cells Cultured Membrane potential Ethanol Dose-Response Relationship Drug Hepatology Dimethyl sulfoxide Biological Transport Molecular biology Rats Quaternary Ammonium Compounds medicine.anatomical_structure Liver Verapamil chemistry Mechanism of action Biochemistry Hepatocyte Cardiovascular agent medicine.symptom medicine.drug |
Zdroj: | Journal of Hepatology. 21:308-314 |
ISSN: | 0168-8278 |
DOI: | 10.1016/s0168-8278(05)80306-x |
Popis: | The effect of ethanol on the hepatic uptake of various cationic drugs was studied in isolated perfused rat livers, isolated rat hepatocytes and isolated rat liver mitochondria. In isolated rat hepatocytes and in isolated perfused rat livers, the uptake of the model organic cation tri-n-butylmethylammonium was found to be markedly stimulated by ethanol in a concentration-dependent fashion. The uptake of tri-n-butylmethylammonium at 1 μ M was increased to 120% and 137% at 0.5% (v/v, (=87 mM)) and 1% (v/v, (=174 mM)) ethanol, respectively. At 25 μ M, tri-n-butylmethylammonium uptake was increased to 124% and 152% at 0.5% (v/v) and 1% (v/v) of ethanol, respectively. The uptake of the organic cations azidoprocainamide methoiodide, vecuronium, ORG 9426 and ORG 6368, the anionic compound taurocholate and the uncharged compound ouabain was not markedly increased at these ethanol concentrations. The mechanism of action of ethanol on the uptake of tri-n-butylmethylammonium was further studied. Competitive inhibitors for the type I organic cation uptake system, procainamide ethobromide and verapamil, almost completely blocked uptake of tri-n-butylmethylammonium (1 μ M) in the presence of 1% (v/v) ethanol, indicating that carrier-mediated uptake is still involved and that additional passive diffusion is unlikely. Neither the plasma membrane potential nor the accumulation of the cation in mitochondria was altered after ethanol treatment, suggesting that potential driving forces for uptake and sequestration were not affected. Apart from ethanol, methanol (1%, v/v), propanol (1%, v/v) and dimethyl sulfoxide (1%, v/v) also stimulated the uptake of tri-n-butylmethylammonium (at 1 μ M) in isolated rat hepatocytes to 117%, 124% and 122% respectively. The results of our study indicate that ethanol selectively stimulates the uptake of the aliphatic organic cation tri-n-butylmethylammonium rather than through generally alterated hepatobiliary transport processes. |
Databáze: | OpenAIRE |
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