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Transport systems of isolated hepatocytes

Studies on the transport of biliary compounds

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Abstract

Hepatocellular transport of some substances with predominantly biliary elimination was studied by use of isolated rat liver cells. Active uptake of the hydrophilic compounds ouabain and cholate proceeded over 10–20 min and the final intracellular concentrations exceeded the extracellular concentrations more than 60-fold. Uptake of both substances was saturable and compatible with carrier-mediation. Uptake of the lipophilic compounds digitoxin and naphthol was not active, terminated within 1 min and compatible with simple diffusion.

The velocity of uptake depended on 3 major parameters: substrate features, cellular factors, and experimental conditions. Substrate features included: lipophilicity or hydrophilicity of the compound. Cellular factors included: presence and activity of transport systems. Experimental conditions included: substrate concentration, amount of cells, composition of medium.

Intracellular conjugation of cholate and naphthol produced the same polar metabolites which are formed in vivo. These metabolites were then in part released from the isolated hepatocytes into the medium. The transport systems for release are more difficult to characterize than those for uptake, and therefore little is known about their nature, despite their importance in detoxication.

If isolated hepatocytes are used in toxicology to assess metabolism or biological effects of foreign compounds, transport across the liver cell membrane is potentially a rate limiting step.

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  1. Institut für Toxikologie, Universität Tübingen, Wilhelmstrasse 56, D-7400, Tübingen, Federal Republic of Germany

    Michael Schwenk

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Schwenk, M. Transport systems of isolated hepatocytes. Arch. Toxicol. 44, 113–126 (1980). https://doi.org/10.1007/BF00303188

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