OATP

Organic Anion Transporting Polypeptide Family (OATP) 

Family Gem Gem symbol Tissues 9 Polarity2 Chromosome Ref. seq./ GenBank 

liver K, kidney B, brain I, small intestine PI, placenta A, adrenal gland Lu, lung. 

Gene Polymorphism Position Effect Function References 

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Cellular defense mechanisms against toxins (A multistep mechanism for elimination of toxic metabolites and xenobiotics. It involves various transport, oxidation, and conjugation steps.) are usually divided into several steps as it is visualized on Fig. 3. Organic anion transporting proteins (OATPs) are responsible for the cellular uptake of endogenous compounds and... 

MDR-ABC Transporters. Figure 3 Detoxification cellular mechanisms. X, toxic compound X-OH, oxidized toxic compound GS-X, conjugated toxic compound OATP, organic anion transporting proteins CYPs, cytochromes GSH, glutathion UDPGIcUA, Uridine 5-diphosphoglucuronic acid PAPs, 3-phosphoadenylylsulfate. 

Tamai I, Nezu J, Uchino H, Sai Y, Oku A, Shimane M, et al. Molecular identification and characterization of novel members of the human organic anion transporter (OATP) family. Biochem Biophys Res Commun 2000 273 251-60. 

In cell lines, the organic anion transporters (OAT and OATP) have been identified and cloned into cells of kidney origin such as LLC-PK1, MDCK, HK-2, and Caco-2 [129]. The most well-known uptake transporters, which transport the substrate over the membrane into the organism are the amino acid- [35, 42, 139] and oligopeptide-carriers (PepTl and PepT2) [139-142]. These two transporter families are abundantly expressed in the small intestine of most animals, and can therefore be involved in the absorption process of pharmaceutical drugs. The PepTl is expressed in the cell lines Caco-2 and HT-29 [140-142]. 

M. F., Wilkinson, G. R., Kim, R. B., OATP and P-glycoprotein transporters mediate the cellular uptake and excretion of fexofenadine, Drug Metab. Dispos. 1999, 27, 866-871. 

Organic anion transporters can be divided into three major families organic anion transporters (OATs), organic anion transporting polypeptides (OATPs), and multidrug resistance associated proteins (MRPs) [201]. 

St-Pierre, M. V., etal. Characterization of an organic anion-transporting polypeptide (OATP-B) in human placenta. J. Clin. Endocrinol. Metab. 2002, 87, 1856-1863. 

In addition to OATP/Oatp family proteins, some of the organic anion transporter (OAT) family proteins may be responsible for hepatic uptake. Although many OAT family proteins are expressed in the kidney [36], human and rat OAT2 is also expressed in the liver [37, 38]. Human OAT2 transports p-amino-... 

In contrast, some Type II cations, such as N-(4,4-azo-n-pentyl)-21-deoxy-ajmalinium and rocuronium, have been shown to be transported by rat Oatp 2 [64—66]. Since human OATP2 or OATP8 cannot transport organic cations [53], the molecular mechanism for the uptake of Type II cations (e.g., rocuronium) into isolated human hepatocytes [11] remains to be clarified. Although human OATP-A transports rocuronium, its hepatic expression is minimal [66]. 

R., Pizzagalli, F., Fattinger, K., Meier, P. J., Hagenbuch, B., Organic anion-transporting polypeptide B (OATP-B) and its functional comparison with three other OATPs of human liver, Gastroenterology 2001, 120, 525-533. 

Tamai, I., Nozawa, T., Koshida, M., Nezu, J., Sai, Y., Tsuji, A., Functional characterization of human organic anion transporting polypeptide B (OATP-B) in comparison with liver-specific OATP-C, Pharm. Res. 2001, 18, 1262-1269. 

Tirona, R. G., Leake, B. F., Merino, G., Kim, R. B., Polymorphisms in OATP-C identification of multiple allelic variants associated with altered transport activity among European-and African-Americans, J. Bid. Chem. 2001, 276, 35669-35675. 

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