Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2021:266:81-100.
doi: 10.1007/164_2021_450.

Genetic and Epigenetic Regulation of Organic Cation Transporters

Charlotte Kölz  1   2 , Elke Schaeffeler  1   2   3 , Matthias Schwab  1   2   3   4 , Anne T Nies  5   6   7
Affiliations
Review

Genetic and Epigenetic Regulation of Organic Cation Transporters

Charlotte Kölz et al. Handb Exp Pharmacol. 2021.

Abstract

Organic cation transporters (OCTs) of the solute carrier family (SLC) 22 are the subject of intensive research because they mediate the transport of many clinically-relevant drugs such as the antidiabetic agent metformin, the opioid tramadol, and the antimigraine agent sumatriptan. OCT1 (SLC22A1) and OCT2 (SLC22A2) are highly expressed in human liver and kidney, respectively, while OCT3 (SLC22A3) shows a broader tissue distribution. As suggested from studies using knockout mice, particularly OCT2 and OCT3 appear to be of relevance for brain physiological function and drug response. The knowledge of genetic factors and epigenetic modifications affecting function and expression of OCTs is important for a better understanding of disease mechanisms and for personalized treatment of patients. This review briefly summarizes the impact of genetic variants and epigenetic regulation of OCTs in general. A comprehensive overview is given on the consequences of OCT2 and OCT3 knockout in mice and the implications of genetic OCT2 and OCT3 variants on central nervous system function in humans.

Keywords: Brain; Central nervous system; Drug response; Drug transporters; Epigenetics; Genotype–phenotype correlation; Interindividual variability; Knockout mice; OCT1; OCT2; OCT3; Organic cation transport; Pharmacogenomics; Pharmacokinetics; Single nucleotide polymorphisms.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Aoki M, Terada T, Kajiwara M, Ogasawara K, Ikai I, Ogawa O, Katsura T, Inui K-I (2008) Kidney-specific expression of human organic cation transporter 2 (OCT2/SLC22A2) is regulated by DNA methylation. Am J Physiol Ren Physiol 295:F165–F170. https://doi.org/10.1152/ajprenal.90257.2008 - DOI
    1. Aoyama N, Takahashi N, Kitaichi K, Ishihara R, Saito S, Maeno N, Ji X, Takagi K, Sekine Y, Iyo M, Harano M, Komiyama T, Yamada M, Sora I, Ujike H, Iwata N, Inada T, Ozaki N (2006) Association between gene polymorphisms of SLC22A3 and methamphetamine use disorder. Alcohol Clin Exp Res 30:1644–1649. https://doi.org/10.1111/j.1530-0277.2006.00215.x - DOI - PubMed
    1. Bacq A, Balasse L, Biala G, Guiard B, Gardier AM, Schinkel A, Louis F, Vialou V, Martres M-P, Chevarin C, Hamon M, Giros B, Gautron S (2012) Organic cation transporter 2 controls brain norepinephrine and serotonin clearance and antidepressant response. Mol Psychiatry 17:926–939. https://doi.org/10.1038/mp.2011.87 - DOI - PubMed
    1. Baganz NL, Horton RE, Calderon AS, Owens WA, Munn JL, Watts LT, Koldzic-Zivanovic N, Jeske NA, Koek W, Toney GM, Daws LC (2008) Organic cation transporter 3: keeping the brake on extracellular serotonin in serotonin-transporter-deficient mice. Proc Natl Acad Sci U S A 105:18976–18981. https://doi.org/10.1073/pnas.0800466105 - DOI - PubMed - PMC
    1. Baganz N, Horton R, Martin K, Holmes A, Daws LC (2010) Repeated swim impairs serotonin clearance via a corticosterone-sensitive mechanism: organic cation transporter 3, the smoking gun. J Neurosci 30:15185–15195. https://doi.org/10.1523/JNEUROSCI.2740-10.2010 - DOI - PubMed - PMC

LinkOut - more resources