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Despite the similarity of ligand specificity and transport function, the tissue distribution of the three OCTs varies greatly in humans and other species (Fig. 2.1, Table 2.1). Though expressed in many tissues, human OCT1 is most highly expressed in the liver and localized to the basolateral membrane of hepatocytes [1]. In rodents, high expression of OCT1 is also observed on the sinusoidal membrane of hepatocytes [1]. However, the expression and location of OCT1 in the kidney differs between human and rodents. Whereas in rodents, OCT1 is also expressed in the kidney and located on the basolateral membrane of proximal tubules, very low levels of OCT1 mRNA are detected in human kidney [6]. In addition to the expression pattern in the kidney and liver of rodents, Oct1 is also expressed in rodent intestine, and on the basolateral membrane of enterocytes. In contrast, in the trachea and bronchi of human, rat, and mouse, OCT1 appears to be expressed on the luminal membrane of epithelial cells [1]. In addition, low expression levels of hOCT1 have been detected in other tissues including brain, heart, skeletal muscle, peripheral leukocytes, adrenal gland, mammary gland, immune cells, and adipose tissue [7].

FIGURE 2.1 Tissue distribution and membrane localization of organic cation and zwitterion transporters. Created with BioRender.com.

In comparison to OCT1, OCT2 has a more restricted expression pattern. It is most highly expressed in the kidney and is generally considered to be a “kidney‐specific” uptake OCT. In human kidney, OCT2 is expressed in all three segments of the proximal tubules [6], whereas in rat kidney Oct2 is located primarily to the S2 and S3 segments [1]. OCT2 is localized to the basolateral membrane of renal and intestinal epithelial cells [2]. In the lung, OCT2, like OCT1, is expressed at low levels on the luminal membrane of airway epithelia [1]. In brain, OCT2 (and OCT1) is expressed on the apical side of brain microvessel endothelial cells from humans, rats, and mice [8]. Low levels of expression of OCT2 have also been reported in brain parenchyma, thymus, placenta, and the inner ear [7].

In contrast to OCT1‐2, OCT3 has a wider tissue distribution with relatively high expression levels in skeletal muscle, placenta, salivary glands, heart, brain, adrenal gland, trachea, small intestine, and uterus [7]. The human OCT3 is also expressed in tumors and cancer cell lines [1]. In rodents, expression of Oct3 has been detected in additional organs, as well as Sertoli cells and basophile granulocytes [1]. The subcellular localization of OCT3 is tissue‐specific. OCT3 is localized to the basolateral membrane of the trophoblast in placenta and to the sinusoidal membrane of hepatocytes; whereas in the lung and intestine, it is localized to the apical membrane of epithelial cells [1, 7]. OCT3 has been observed in multiple brain regions in rodents, including the hippocampus, area postrema, subfornical organ, medial hypothalamus, and ependym of the third ventricle [1] and may serve as a low‐affinity reuptake transporter for neurotransmitters. In salivary glands, the OCT3 protein is localized to both basolateral and apical membranes of the secretory epithelial cells [9].

TABLE 2.1 Tissue distribution of organic cation and zwitterion transporters in humans [1–5]

Gene	Protein	Human tissue distribution
SLC22A1	OCT1	Liver, stomach, intestine, colon, spleen, trachea, lung, urinary bladder, skeletal muscle, heart, brain, mammary gland, leukocytes, epithelial cells, placenta, adrenal gland, skin, adipose, kidney
SLC22A2	OCT2	Kidney, intestine, lung, skin, brain, choroid plexus, spleen, trachea, placenta, thymus, inner ear, epithelial cells, neurons
SLC22A3	OCT3	Ubiquitous. Skeletal muscle, heart, placenta, uterus, salivary glands, adipose, adrenal gland, intestine, colon, brain, trachea, lung, liver, urinary bladder, kidney, skin, blood, vessels, mammary gland, epithelial cells, neurons
SLC19A2	THTR‐1	Ubiquitous. Skeletal muscle, placenta, heart, liver, kidney, brain, lung, intestine, pancreas, bone marrow, ear
SLC19A3	THTR‐2	Intestine, placenta, lung, kidney, liver, brain, adipose
SLC29A4	PMAT	Brain, skeletal muscle, heart, kidney, liver, intestine
SLC22A4	OCTN1	Ubiquitous. Whole blood, spleen, fibroblasts, reproductive tissues, brain, lung, small intestine, skeletal muscle, kidney
SLC22A5	OCTN2	Ubiquitous. Skeletal muscle, brain, prostate, kidney, thyroid, reproductive tissues, small intestine, colon, skin, artery, nerve, breast, adipose, stomach, lung, heart, liver
SLC22A15	SLC22A15	Ubiquitous. Brain, lung, bone marrow, whole blood
SLC22A16	CT2	Testis, kidney, bone marrow, whole blood