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Abstract

Mechanisms for the hepatic uptake of organic cations. Studies with the muscle relaxant vecuronium in isolated rat hepatocytes.

W E Mol, G N Fokkema, B Weert and D K Meijer
Journal of Pharmacology and Experimental Therapeutics January 1988, 244 (1) 268-275;
W E Mol
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G N Fokkema
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B Weert
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D K Meijer
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Abstract

In hepatobiliary transport of organic cations some remarkable differences have been reported between the monovalent compounds (prototype procainamidethobromide) and the potentially bivalent cations, containing a second quaternary ammonium group or a protonated tertiary amine function (prototype d-tubocurarine). In order to characterize the hepatic uptake mechanism for such bivalent cations in more detail, we studied the uptake of the steroidal muscle relaxant vecuronium in isolated rat hepatocytes. Uptake occurred by both a saturable (Vmax = 181 pmol/min x 10(6) cells, Km = 15 microM) and a nonsaturable process (rate constant = 1.10 pmol/min/10(6) cells/microM). The uptake of vecuronium was reduced by various metabolic inhibitors and by sulfhydryl-blocking agents. The transport system showed temperature dependency with an activation energy of 85 kJ/mol. Sodium replacement by lithium or choline in the extracellular medium had no effect on the uptake of vecuronium. Replacement of sodium chloride by sucrose led to a decrease of the uptake, whereas chloride replacement by bicarbonate or iodide stimulated the vecuronium uptake. These data point to a significant anion-dependency of the uptake system and indicate electroneutral uptake of vecuronium. The uptake of vecuronium was inhibited by a variety of hepatic transport model compounds, including bile acids, uncharged compounds and high molecular weight organic cations. Low molecular weight monovalent cations had no effect on the uptake of vecuronium.(ABSTRACT TRUNCATED AT 250 WORDS)

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Journal of Pharmacology and Experimental Therapeutics
Vol. 244, Issue 1
1 Jan 1988
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Abstract

Mechanisms for the hepatic uptake of organic cations. Studies with the muscle relaxant vecuronium in isolated rat hepatocytes.

W E Mol, G N Fokkema, B Weert and D K Meijer
Journal of Pharmacology and Experimental Therapeutics January 1, 1988, 244 (1) 268-275;

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Abstract

Mechanisms for the hepatic uptake of organic cations. Studies with the muscle relaxant vecuronium in isolated rat hepatocytes.

W E Mol, G N Fokkema, B Weert and D K Meijer
Journal of Pharmacology and Experimental Therapeutics January 1, 1988, 244 (1) 268-275;
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