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Extraneuronal noradrenaline transport (uptake2) in a human cell line (Caki-1 cells)

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Summary

This study describes for the first time an experimental system for the extraneuronal transport mechanism of noradrenaline (uptake2) which is based on a clonal cell line (Caki-1). Caki-1 cells were originally derived from a human renal cell carcinoma. The conclusion that these cells express uptake2 is supported by several experimental findings. (1) The initial rate of 3H-noradrenaline uptake in Caki-1 cells is saturable, the K m being 450 μmol/l. (2) Inhibitors of uptake2 such as corticosterone (1 μmol/l) and O-methyl-isoprenaline (100 Eμmol/l) largely inhibit 3H-noradrenaline uptake in Caki-1 cells. Whereas inhibitors of the neuronal transport mechanism for noradrenaline (uptake1) such as desipramine (1 μmol/l) and cocaine (10 μmol/l) do not reduce it. (3) Depolarization of Caki-1 cells by the elevation of extracellular potassium inhibits 3H-noradrenaline uptake. (4) There is a highly significant correlation between the IC50's of various compounds for the inhibition of 3H-noradrenaline uptake in Caki-1 cells and rabbit aorta known to possess uptake2.

Interestingly enough, uptake2 in Caki-1 cells and rabbit aorta is inhibited by cimetidine, quinidine and procainamide which are substrates of the renal transport mechanism for organic cations. Moreover, 3H-cimetidine is shown to be a substrate of uptake2 in the isolated perfused rat heart. These results indicate a striking similarity between uptake2 and the renal transport mechanism for organic cations.

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Authors and Affiliations

  1. Institut für Pharmakologie und Toxikologie, Universität Würzburg, Versbacher Strasse 9, 8700, Wurzburg, Federal Republic of Germany

    E. Schömig & C. L. Schönfeld

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  1. E. Schömig
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  2. C. L. Schönfeld
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Send offprint requests to E. Schömig at the above address

Supported by the Deutsche Forschungsgemeinschaft (SFB 176, Scho 373) and the Dr. Robert Pfleger Stiftung

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Schömig, E., Schönfeld, C.L. Extraneuronal noradrenaline transport (uptake2) in a human cell line (Caki-1 cells). Naunyn-Schmiedeberg's Arch Pharmacol 341, 404–410 (1990). https://doi.org/10.1007/BF00176331

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  • DOI: https://doi.org/10.1007/BF00176331

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