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Transepithelial Transport and Metabolism of Thyrotropin-Releasing Hormone (TRH) in Monolayers of a Human Intestinal Cell Line (Caco-2): Evidence for an Active Transport Component?

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Abstract

Cell culture models for gastrointestinal transport and metabolism are important mechanistic tools. Our studies of Caco-2 monolayers demonstrate heterogeneity in transport characteristics depending on passage number and origin of the cells. In accordance with data obtained in animals and humans, TRH shows a carrier-mediated, saturable transport component, which operates parallel to a passive pathway in Caco-2 cells at passage number 89-99. At low TRH concentrations (<3 mM) active transport becomes prominent, as demonstrated by the temperature dependence of TRH transport and inhibition experiments. The Michaelis-Menten parameters of the active, saturable transport component are: Km = 1.59 mM and Vmax = 1.84 µM/min. The pH optimum was determined to be at pH 6.0. On the other hand an exclusively paracellular passive route was found with Caco-2 cells at passage number 30-34. These results are also in agreement with observations made by others in cell culture experiments. The aspect of rigorously characterizing the specific Caco-2 clone under investigation is emphasized, especially when active transport mechanisms are suspected.

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  1. Department of Pharmaceutics and Biopharmacy, University of Marburg, D-35032, Marburg, Germany

    Elke Walter & Thomas Kissel

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  1. Elke Walter
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Walter, E., Kissel, T. Transepithelial Transport and Metabolism of Thyrotropin-Releasing Hormone (TRH) in Monolayers of a Human Intestinal Cell Line (Caco-2): Evidence for an Active Transport Component?. Pharm Res 11, 1575–1580 (1994). https://doi.org/10.1023/A:1018953603301

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