The SLC22 family with transporters of organic cations, anions and zwitterions

Mol Aspects Med. Apr-Jun 2013;34(2-3):413-35. doi: 10.1016/j.mam.2012.10.010.

Abstract

The SLC22 family contains 13 functionally characterized human plasma membrane proteins each with 12 predicted α-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, α-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.

Publication types

  • Review

MeSH terms

  • Absorption
  • Brain / metabolism
  • Carnitine / metabolism
  • Humans
  • Intestine, Small / metabolism*
  • Ion Pumps / genetics*
  • Ion Pumps / metabolism
  • Ion Pumps / physiology*
  • Ketoglutaric Acids / metabolism
  • Kidney / metabolism
  • Liver / metabolism
  • Models, Molecular*
  • Multigene Family / genetics*
  • Neurotransmitter Agents / metabolism
  • Nucleotides, Cyclic / metabolism
  • Organic Cation Transport Proteins / metabolism
  • Organic Cation Transporter 1 / metabolism
  • Organic Cation Transporter 2
  • Prostaglandins / metabolism
  • Protein Conformation*
  • Uric Acid / metabolism

Substances

  • Ion Pumps
  • Ketoglutaric Acids
  • Neurotransmitter Agents
  • Nucleotides, Cyclic
  • Organic Cation Transport Proteins
  • Organic Cation Transporter 1
  • Organic Cation Transporter 2
  • Prostaglandins
  • SLC22A2 protein, human
  • solute carrier family 22 (organic cation transporter), member 3
  • Uric Acid
  • Carnitine