Organic human OATP

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]. 

The organic anion transporting polypeptides (rodents Oatps human OATPs) represent a family of proteins responsible for the membrane transport of a large number of endogenous and xenobiotic compounds with diverse chemical characteristics. Since the first expression of Oatplal in 1994, organic anion transporting polypeptide family members have been isolated from a variety of tissues in vertebrate animal species [1]. 

The organic anion transporters (human OATs, rodent oats) are classified within the SLC22A solute carrier family, and the transporting peptides (human OATPs, rodent... 

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. 

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-... 

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. 

Pizzagalli F, Hagenbuch B, Bottom-ley KM, Meier PJ. Identification of a new human organic anion transporting polypeptide OATP-F. GenBank Accession No AF260704 2001. 

There have been several studies that underscore the importance of unbound concentration in cell-based studies of receptor function. In a model study of the effect of plasma protein binding on the renal transport of organic anions using the expression of various organic anion transporters (OATPs) in Xenopus oocytes, the transport of ochratoxin A, methotrexate, and estrone sulfate was found to be strongly inhibited by the addition of human serum albumin to the culture medium [16]. Similarly, the addition of oq-acid glycoprotein was found to reverse the blockade of sodium-ion current by cocaine in a preparation of cardiac myocytes [17]. 

Campbell, S.D., de Morais, S.M. and Xu, J.J. (2004) Inhibition of human organic anion transporting polypeptide OATP 1B1 as a mechanism of drug-induced hyperbilirubinemia. Chemico-Biological Interactions, 150, 179-187. 

D. Kobayashi, T. Nozawa, K. Imai, J. Nezu, A. Tsuji, and I. Tamai. Involvement of human organic anion transporting polypeptide OATP-B (SLC21A9) in pH-dependent transport across intestinal apical membrane. J Pharmacol Exp Ther 306 703-708 (2003). 

Nozawa, T., Nakajima, M., Tamai, I., et al. (2002) Genetic polymorphisms of human organic anion transporters OATP-C (SLC21A6) and OATP-B (SLC21A9) allele frequencies in the Japanese population and functional analysis. J. Pharmacol. Exp. Ther. 302, 804-813. 

Satoh H, Yamashita F, Tsujimoto M, et al. Citrus juices inhibit the function of human organic anion transporting polypeptide OATP-B. Drug Metab Dispos 2005 33(4) 518-253. 

---