Info OCT (SLC22) transporters

The OCTs of the human SLC22 family include three potential sensitive proteins (OCT1, OCT2, and OCT3) and three H + -driven transporters of carnitine and/or cations (OCTN1, OCTN2, and CT2, also known as SLC22A4, SLC22A5, and either FLIPT2 or SLC22A16, respectively). Like most members of the SLC22 family they have 12 TMDs. The amino and carboxyl termini are cytoplasmic and the proteins have glycosylated extracellular loops and intracellular loops that contain phosphorylation sites (Figure 6).

OCT1 and OCT2 were originally cloned from the rat kidney80,81; the human homologs were then isolated and OCT3 cloned.82 Both OCT1 and OCT2 lie in the basolateral membranes of epithelial cells, but there is no conclusive evidence as to whether OCT3 is located in the basolateral or apical membrane of polarized cells. The substrate and inhibitor specificities of OCT1, OCT2, and OCT3 overlap extensively, but the OCT subtypes differ significantly in their affinity and maximal transport rates. All three OCTs recognize a variety of organic cations (OCs), including endogenous bioactive amines such as acetylcholine, choline, epinephrine, norepinephrine, dopamine, and serotonin, and drugs like cimetidine, quinine, quinidine, prazosin, desipramine, verapamil, and morphine. Some uncharged compounds and anions are also transported, such as some anionic prostaglandins.83 The nitrogen moiety of the weak bases bears a net positive charge at physiological pH, allowing electrostatic interaction with the binding sites of the OCTs. The 'type 1' and 'type 2' classifications of OCs were developed to study their uptake by the liver.84 Type 1 OCs are small (60-350 Da), monovalent, hydrophilic compounds such as tetraethylammonium (TEA) and the parkinsonian neurotoxin 1-methyl-4-phenyl pyridinium (MPP+). In contrast, type 2 OCs are usually bulkier (>500 Da; e.g., anthracyclines) and polyvalent (e.g., d-tubocurarine). This classification helps to differentiate the mechanisms by which they are transported across polarized cells. Type 2 OCs are believed to diffuse across the basolateral membrane and to be exported across the apical membrane by MDR1. In contrast, the basolateral entry of type 1 OCs involves one or more transporters, including OCT1, 2, and 3, and their efflux at the apex may be mediated by OCTN 1 and 2. The OCTs generally mediate bidirectional transport of substrate molecules, and this depends mainly on the membrane potential and not directly on the transmembrane gradients of Na+ or H +. There is thus an electrogenic facilitated diffusion of the monovalent cations in a direction that is defined by the prevailing electrical and chemical (i.e., substrate concentration) gradients across the membrane.86

Both OCT1 and OCT2 are found primarily in the major excretory organs (the kidney and the liver) and to a lesser extent in the intestine and the brain. OCT1 is highly species-specific. Human OCT1 is most abundant in the liver, where it mediates the uptake of type1 OCs across the sinusoidal membrane of hepatocytes; it is less abundant in the

Table 6 Current human concentrative and equilibrative nucleoside transporters, SLC28 and SLC29 gene nomenclature and properties

Human gene




Transport mode and

Tissue distribution




name (aliases)


energy source

(cellular expression)

transport impact

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