Multispecific organic anion transporter cMOAT

Kawakami, M., Kagotani, K., Okumura, K., Akiyama, S., Kuwano, M., A human canalicular multispecific organic anion transporter (cMOAT) gene is overexpressed in cisplatin-resistant human cancer cell lines with decreased drug accumulation, Cancer Res. 1996, 56, 4124-4129. 

Wada M, Toh S, Taniguchi K, Nakamura T, Uchiumi T, Kohno K et al. Mutations in the canalicular multispecific organic anion transporter (cMOAT) gene, a novel ABC transporter, in patients with hyperbilirubinemia I I/Dubin-Johnson syndrome. Hum Mol Genet 1998 7(2) 203-207. 

Both irinotecan and SN-38 are primarily excreted into the bile by the canalicular multispecific organic anion transporter (cMOAT), a member of the ATP cassette of transporters. Therefore, inhibitors of cMOAT, such as ciclosporin, can reduce the clearance of irinotecan and SN-38 (41,42). 

Kawabe, T, Chen, Z.S., Wada, M., Uchiumi, T., Ono, M., Akiyama, S. et al. (1999) Enhanced transport of anticancer agents and leukotriene C4 hy the human canalicular multispecific organic anion transporter (cMOAT/MRP2). FEBS Letters, 456 (2), 327-331. 

Courtois A, Payen E, Vernhet E, Morel P, Guillouzo A, Pardel 0. Differential regulation of canalicular multispecific organic anion transporter (cMOAT) expression by the chemopreventive agent oltipraz in primary rat hepatocytes and in rat liver. Carcinogenesis 1999 20 2327-2330. 

Yamazaki M, Akiyama S, Ni inuma K, Nishigaki R, Sugiyama Y. Biliary excretion of pravastatin in rats contribution of the excretion pathway mediated by canalicular multispecific organic anion transporter (cMOAT). Drug Metab Dispos 1997 25 1123-1129. 

These metabolites are later excreted into the bile via the canalicular multispecific organic anion transporter (cMOAT) and subsequently re-metabohzed by the intestinal flora. This enterohepatic recirculation is responsible for the slow terminal plasma clearance of GE. However, the major elimination pathway for GA is in feces [1,2]. The summary of the pharmacokinetics of GA is depicted in Fig. 126.2. 

C. C. Paulusma, R. P. Oude Elferink et al. Drug export activity of the human canalicular multispecific organic anion transporter in polarized kidney MDCK cells expressing cMOAT (MRP2) cDNA, J. Clin. Invest. 1998, 101, 1310-1319... 

Toh S, Wada M, Uchiumi T, Inokuchi A, Makino Y, Horie Y et al. Genomic structure of the canalicular multispecific organic anion-transporter gene (MRP2/ cMOAT) and mutations in the ATP-bind-ing-cassette region in Dubin-Johnson syndrome. Am J Hum Genet 1999 64(3)739-746. 

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