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Uptake Transporters of the Human OATP Family

Molecular Characteristics, Substrates, Their Role in Drug–Drug Interactions, and Functional Consequences of Polymorphisms

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Book cover Drug Transporters

Part of the book series: Handbook of Experimental Pharmacology ((HEP,volume 201))

Abstract

Organic anion transporting polypeptides (OATPs, gene family: SLC21/SLCO) mediate the uptake of a broad range of substrates including several widely prescribed drugs into cells. Drug substrates for members of the human OATP family include HMG-CoA-reductase inhibitors (statins), antibiotics, anticancer agents, and cardiac glycosides. OATPs are expressed in a variety of different tissues including brain, intestine, liver, and kidney, suggesting that these uptake transporters are important for drug absorption, distribution, and excretion. Because of their wide tissue distribution and broad substrate spectrum, altered transport kinetics, for example, due to drug–drug interactions or due to the functional consequences of genetic variations (polymorphisms), can contribute to the interindividual variability of drug effects. Therefore, the molecular characteristics of human OATP family members, the role of human OATPs in drug–drug interactions, and the in vitro analysis of the functional consequences of genetic variations in SLCO genes encoding OATP proteins are the focus of this chapter.

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Abbreviations

BSP:

Bromosulfophthalein

K m :

Kinetic constant (Michaelis–Menten constant)

OATP:

Organic anion transporting polypeptide

OCT:

Organic cation transporter

SLCO :

Gene of the SLCO family encoding OATP uptake transporters

V max :

Maximal transport velocity

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Acknowledgment

I thank Christina Fahrmayr for critical reading of the manuscript.

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Authors and Affiliations

  1. Institute of Experimental and Clinical Pharmacology and Toxicology, Friedrich-Alexander-University Erlangen-Nuremberg, Fahrstrasse 17, 91054, Erlangen, Germany

    Jörg König

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  1. Jörg König
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  1. Inst. Experimentelle und Klinische, Pharmakologie und Toxikologie, Universität Erlangen-Nürnberg, Fahrstr. 17, Erlangen, 91054, Germany

    Martin F. Fromm

  2. Division of Clinical Pharmacology, University of Western Ontario, Windmere Road 339, London, N6A 5A5, Ontario, Canada

    Richard B. Kim

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König, J. (2011). Uptake Transporters of the Human OATP Family. In: Fromm, M., Kim, R. (eds) Drug Transporters. Handbook of Experimental Pharmacology, vol 201. Springer, Berlin, Heidelberg. https://doi.org/10.1007/978-3-642-14541-4_1

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