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What do drug transporters really do?

Nature Reviews Drug Discovery volume 14, pages 29–44 (2015)Cite this article

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Abstract

Potential drug–drug interactions mediated by the ATP-binding cassette (ABC) transporter and solute carrier (SLC) transporter families are of clinical and regulatory concern. However, the endogenous functions of these drug transporters are not well understood. Discussed here is evidence for the roles of ABC and SLC transporters in the handling of diverse substrates, including metabolites, antioxidants, signalling molecules, hormones, nutrients and neurotransmitters. It is suggested that these transporters may be part of a larger system of remote communication ('remote sensing and signalling') between cells, organs, body fluid compartments and perhaps even separate organisms. This broader view may help to clarify disease mechanisms, drug–metabolite interactions and drug effects relevant to diabetes, chronic kidney disease, metabolic syndrome, hypertension, gout, liver disease, neuropsychiatric disorders, inflammatory syndromes and organ injury, as well as prenatal and postnatal development.

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Figure 1: SLC and ABC drug transporters are expressed in most epithelial barriers.
Figure 2: SLC and ABC drug transporters that have been implicated in the handling of xenobiotics and drugs.
Figure 3: Reconstruction of metabolic networks from large-scale 'omics' data implicates drug transporters in metabolic pathways.

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Acknowledgements

The author gratefully acknowledges the considerable help of W. Wu and K. T. Bush in providing comments, as well as in the preparation of figures, tables and references. Also, the author is indebted to students, postdoctoral fellows and many colleagues within and outside the general field of drug transporters for stimulating discussions. Given the broad scope of this subject, it was not possible to discuss many important papers, and there is a risk of oversimplification; the reader can therefore refer to more specialized authoritative reviews such as those cited in this article. This work was partly supported by the US National Institutes of Health Grants (GM098449, GM104098 and HD07160 (U54)).

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  1. Departments of Pediatrics, Medicine, and Cellular and Molecular Medicine, University of California, San Diego, 9500 Gilman Drive, La Jolla, 92093-0693, California, USA

    Sanjay K. Nigam

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Correspondence to Sanjay K. Nigam.

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The author has received research support from pharmaceutical companies.

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Nigam, S. What do drug transporters really do?. Nat Rev Drug Discov 14, 29–44 (2015). https://doi.org/10.1038/nrd4461

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