Pharmacological and physiological functions of the polyspecific organic cation transporters: OCT1, 2, and 3 (SLC22A1-3).
For the elimination of environmental toxins and metabolic waste products, the body is equipped with a range of broad-specificity transporters that are generally present in the liver, kidney, and intestine. The polyspecific organic cation transporters OCT1, 2, and 3 (SLC22A1-3) mediate the facilitated transport of a variety of structurally diverse organic cations, including many drugs, toxins, and endogenous compounds. OCT1 and OCT2 are found in the basolateral membrane of hepatocytes, enterocytes, and renal proximal tubular cells. OCT3 has a more widespread tissue distribution and is considered to be the major component of the extraneuronal monoamine transport system (or uptake-2), which is responsible for the peripheral elimination of monoamine neurotransmitters. Studies with knockout mouse models have directly demonstrated that these transporters can have a major impact on the pharmacological behavior of various substrate organic cations. The recent identification of polymorphic genetic variants of human OCT1 and OCT2 that severely affect transport activity thus suggests that some of the interpatient differences in response and sensitivity to cationic drugs may be caused by variable activity of these transporters.
The Netherlands Cancer Institute, Division of Experimental Therapy, Amsterdam, The Netherlands. h.jonker@nki.nl
Johan W
JW
Jonker
Alfred H
AH
Schinkel
D017398:Alternative Splicing; D000818:Animals; D001692:Biological Transport; D002395:Catecholamines / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D050813:Octamer Transcription Factor-2; D050814:Octamer Transcription Factor-3; D027702:Organic Cation Transporter 1 / Q000235:genetics / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000502:physiology*
D002395:Catecholamines; D004268:DNA-Binding Proteins; D008565:Membrane Proteins; D050813:Octamer Transcription Factor-2; D050814:Octamer Transcription Factor-3; D027702:Organic Cation Transporter 1; C058435:POU2F2 protein, human; C494173:POU5F1 protein, human; C489206:Pou2f2 protein, mouse; D014157:Transcription Factors