Journal
MOLECULAR ASPECTS OF MEDICINE
Volume 34, Issue 2-3, Pages 413-435Publisher
ELSEVIER
DOI: 10.1016/j.mam.2012.10.010
Keywords
Drug transporter; Cation transporter; Anion transporter; Urate transporter; SLC22; Drug excretion
Funding
- Swiss National Science Foundation through the National Center of Competence in Research (NCCR) TransCure, University of Bern, Switzerland
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The SLC22 family contains 13 functionally characterized human plasma membrane proteins each with 12 predicted alpha-helical transmembrane domains. The family comprises organic cation transporters (OCTs), organic zwitterion/cation transporters (OCTNs), and organic anion transporters (OATs). The transporters operate as (1) uniporters which mediate facilitated diffusion (OCTs, OCTNs), (2) anion exchangers (OATs), and (3) Na+/zwitterion cotransporters (OCTNs). They participate in small intestinal absorption and hepatic and renal excretion of drugs, xenobiotics and endogenous compounds and perform homeostatic functions in brain and heart. Important endogeneous substrates include monoamine neurotransmitters, L-carnitine, alpha-ketoglutarate, cAMP, cGMP, prostaglandins, and urate. It has been shown that mutations of the SLC22 genes encoding these transporters cause specific diseases like primary systemic carnitine deficiency and idiopathic renal hypouricemia and are correlated with diseases such as Crohn's disease and gout. Drug-drug interactions at individual transporters may change pharmacokinetics and toxicities of drugs. (C) 2012 Elsevier Ltd. All rights reserved.
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