Mammalian kidney and liver are critical in maintaining physiological ionic environment. Kidney specializes in removing toxins, drugs, and other organic cations from the blood by a process called "renal secretion". Organic solutes must enter the cell (influx) via the basolateral membrane, move inside the cells, and then transported into the lumen across the apical membrane (efflux). Functional studies have identified two distinct categories of organic cation transporters (OCTs): a system driven by transmembrane potential difference that governs the influx of cations, whereas the H+-gradient-dependent transport system may mediate the efflux of cations. Several multispecific, potential-sensitive transporters (OCT1-3) and H+-dependent transporters (OCTN1-3) have been cloned and characterized from various tissues. OCT superfamily of proteins shares high degree of sequence homology, display 12 transmembrane domains with cytoplasmic N and C-terminus.

OCT1 (rat/mouse 556 aa, ~95% homology; human 554 aa, ~78% homology with rat OCT1) is expressed primarily in the kidney, liver, and intestine. Rat OCT1 has been localized to the basolateral membrane of small intestinal enterocytes, hepatocytes, and S1 segment of the proximal renal tubules. OCT1 mediated uptake of tetraethylammonium (TEA) was pH and Na+-independent and was reduced when membrane potential decreased. OCT1 also transported NMN, choline, MPP, dopamine, thiamine, noradrenaline, histamine, and spermine but not for putrescine.

Rat OCT2 was initially cloned from kidney by homology screening. OCT2 (rat 593 aa, mouse 553 aa, human 555 aa) shares ~70% homology with OCT1. In rat, it is expressed primarily in kidney, and traces were found in colon stomach, and brain. Rat OCT2 has been localized to the basolateral membrane of S2 and S3 segments of proximal tubules. In contrast, OCT2 was localized to the luminal membranes of distal tubule. OCT2 mediates uptake of a variety of cations.

OCT3 (rat/mouse 551 aa; human 556 aa) share 30% homology with OCT1 and 51% with OCT2. It is most abundant in rat placenta, and moderate in the intestine, heart, and brain.
OCT3 expression is very low in kidney and lung and is undetectable in the liver. OCT3 recognized TEA and guanidine along with other cations including neurotoxin (MPP0, neurotransmitter dopamine, and steroids. OCT3 has been identified as extraneuronal monoamine transporter (uptake2).

Some other transporters (NKT and RST from mouse kidney and NLT from rat liver) with sequence homology to OCT have been cloned but their functional characteristics are not established.

Recently a novel transporter termed OCTN1, has been cloned and characterized human fetal liver, which carries a nucleotide birding site motif. OCTN1 (human 551 a, mouse 553 aa) shares ~32% homology with OCT1-3. It is strongly expressed in adult kidney, trachea, bone marrow, and fetal liver, and several tumor cells, but not in adult human liver. OCTN1 mediated uptake of TEA in pH dependent manner.

OCTN2, a structural homolog of OCTN1, has been identified as carnitine transporter. OCTN2 (human/rat/mouse 557 aa) shares ~76% homology with OCTN1. It is strongly expressed in human kidney, skeletal muscle, heart, and placental in adult humans. In rat, OCTN2 expression was found in the proximal and distal tubules and in the glomeruli in the kidney, in the myocardium, valves, and arterioles in the heart, in the labyrinthine layer of the placenta, and brain (cortex, hippocampus, and cerebellum). OCTN2 mediated uptake of carnitine in a Na+-dependant manner, whereas other organic cations were transported without Na+.

OCTN3 (564 aa) has been cloned from mouse testes. It appears to be a carnitine transporter. However, its functional characteristics have not been reported.

ADI has produced highly specific rabbit antibodies for OCT1-3 and OCTN1-3 using antigenic peptide sequences unique to each protein. These antibodies do not crossreact with each other and can be used to study various transporters. Respective antigenic or control peptides are also available to confirm specificity of antibodies.