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• W2034122854 abstract "1 The liver has an important role in the detoxification of organic cations from the circulation. [3H]-1-methyl-4-phenylpyridinium ([3H]-MPP+), a low molecular weight organic cation, is efficiently taken up and accumulated by rat hepatocytes through mechanisms partially unknown. 2 The aim of the present work was to characterize further the uptake of MPP+ by rat isolated hepatocytes. The putative interactions of a wide range of drugs, including inhibitors/substrates of P-glycoprotein, were studied. 3 The uptake of MPP+ was investigated in rat freshly isolated hepatocytes (incubated in Krebs-Henseleit medium with 200 nM [3H]-MPP+ for 5 min) and in the rat liver in situ (perfused with Krebs-Henseleit/BSA medium with 200 nM [3H]-MPP+ for 30 min). [3H]-MPP+ accumulation in the cells and in tissue was determined by liquid scintillation counting. 4 Verapamil (100 μm), quinidine (100 μm), amiloride (1 mM), (+)-tubocurarine (100 μm), vecuronium (45 μm), bilirubin (200 μm), progesterone (200 μm), daunomycin (100 μm), vinblastine (100 μm), cyclosporin A (100 μm) and cimetidine (100 μm) had a significant inhibitory effect on the accumulation of [3H]-MPP+ in isolated hepatocytes. Tetraethylammonium (100 μm) had no effect. 5 In the rat perfused liver, both cyclosporin A (100 μm) and verapamil (100 μm) had much less marked inhibitory effects as compared to their effects on isolated hepatocytes (0% against 35% and 45% against 96% of inhibition, respectively). 6 Inhibition of alkaline phosphatase activity by increasing or decreasing the pH of the incubation medium or by the presence of vanadate (1 mM) or homoarginine (500 μm) led to a significant increase in the accumulation of [3H]-MPP+ in isolated hepatocytes. 7 It was concluded that, in addition to the type I organic cation hepatic transporter, [3H]-MPP+ is taken up by rat isolated hepatocytes through P-glycoprotein, a canalicular transport system that usually excretes endobiotics and xenobiotics. We proposed that the reversal of transport through P-glycoprotein may be related to the loss of efficiency of alkaline phosphatase in isolated hepatocytes." @default.
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• W2034122854 date "1996-12-01" @default.
• W2034122854 modified "2023-10-17" @default.
• W2034122854 title "Inward transport of [3H]-1-methyl-4-phenylpyridinium in rat isolated hepatocytes: putative involvement of a P-glycoprotein transporter" @default.
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• W2034122854 doi "https://doi.org/10.1111/j.1476-5381.1996.tb16067.x" @default.
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