Organic anion transporting polypeptides expressed in liver and brain mediate uptake of microcystin

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2005
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Fischer, Werner Jürgen
Altheimer, Sylvia
Cattori, Valentino
Meier, Peter J.
Hagenbuch, Bruno
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Toxicology and Applied Pharmacology. 2005, 203(3), pp. 257-263. ISSN 0041-008X. Available under: doi: 10.1016/j.taap.2004.08.012
Zusammenfassung

Microcystins are toxins produced by freshwater cyanobacteria. They are cyclic heptapeptides that exhibit hepato- and neurotoxicity. However, the transport systems that mediate uptake of microcystins into hepatocytes and across the blood brain barrier have not yet been identified. Using the Xenopus laevis oocyte expression system we tested whether members of the organic anion transporting polypeptide superfamily (rodent: Oatps; human: OATPs) are involved in transport of the most common microcystin variant microcystin-LR by measuring uptake of a radiolabeled derivative dihydromicrocystin-LR. Among the tested Oatps/OATPs, rat Oatp1b2, human OATP1B1, human OATP1B3, and human OATP1A2 transported microcystin-LR 2- to 5-fold above water-injected control oocytes. This microcystin-LR transport was inhibited by co-incubation with the known Oatp/OATP substrates taurocholate (TC) and bromosulfophthalein (BSP). Microcystin-LR transport mediated by the human OATPs was further characterized and showed saturability with increasing microcystin-LR concentrations. The apparent Km values amounted to 7 ± 3 μM for OATP1B1, 9 ± 3 μM for OATP1B3, and 20 ± 8 μM for OATP1A2. No microcystin-LR transport was observed in oocytes expressing Oatp1a1, Oatp1a4, and OATP2B1. These results may explain some of the observed organ-specific toxicity of microcystin-LR. Oatp1b2, OATP1B1, and OATP1B3 are responsible for microcystin transport into hepatocytes, whereas OATP1A2 mediates microcystin-LR transport across the blood brain barrier.

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570 Biowissenschaften, Biologie
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Environmental toxins, Natural toxins, Microcystin, Cyanobacteria, Blood brain barrier, Hepatocyte, Organic anion transport, Oatp, OATP
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ISO 690FISCHER, Werner Jürgen, Sylvia ALTHEIMER, Valentino CATTORI, Peter J. MEIER, Daniel R. DIETRICH, Bruno HAGENBUCH, 2005. Organic anion transporting polypeptides expressed in liver and brain mediate uptake of microcystin. In: Toxicology and Applied Pharmacology. 2005, 203(3), pp. 257-263. ISSN 0041-008X. Available under: doi: 10.1016/j.taap.2004.08.012
BibTex
@article{Fischer2005Organ-7800,
  year={2005},
  doi={10.1016/j.taap.2004.08.012},
  title={Organic anion transporting polypeptides expressed in liver and brain mediate uptake of microcystin},
  number={3},
  volume={203},
  issn={0041-008X},
  journal={Toxicology and Applied Pharmacology},
  pages={257--263},
  author={Fischer, Werner Jürgen and Altheimer, Sylvia and Cattori, Valentino and Meier, Peter J. and Dietrich, Daniel R. and Hagenbuch, Bruno}
}
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