Methotrexate organic anion transport

Organic anion transporters OAT1 PAH, methotrexate, p-lactam antibiotics,... 

Abe, T., et al. LST-2, a human liver-spedfic organic anion transporter, determines methotrexate sensitivity in gastrointestinal cancers. Gastroenterology 2001, 120, 1689—1699. 

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]. 

Takeda M, Khamdang S, Narikawa S, Kimura H, Hosoyamoda M, Cha SH, Sekine T, Endou H. Characterization of methotrexate transport and its drug interactions with human organic anion transporters. J Pharmacol Exp Ther 2002 302 666-671. 

Saito H, Masuda S, Inui K. Cloning and functional characterization of a novel rat organic anion transporter mediating basolateral uptake of methotrexate in the kidney. J Biol Chem 1996 271 20719-20725. 

Nozaki Y, Kusuhara H, Endou H, et al. Quantitative evaluation of the drug-drug interactions between methotrexate and nonsteroidal anti-inflammatory drugs in the renal uptake process based on the contribution of organic anion transporters and reduced folate carrier. J Pharmacol Exp Ther 2004 309 226-234. 

Masuda M, I lzuka Y, Yamazaki M, et al. Methotrexate is excreted into the bile by canalicular multispecific organic anion transporter in rats. Cancer Res 1997 57 (16) 3506-3510. 

In the intestine only few members of the large group of organic anion transporters have been found OAT2 (SLC22A7) and OATP-B (SLC21A9) responsible for the transport of many different compounds (Burck-hardt and Wolff 2000 Tamai et al. 2000 Kobayashi et al. 2003). Drugs like fexofenadine, methotrexate, pravastatin and ouabain are substrates of OATP s (Cvetkovic et al. 1999 Abe et al. 2001 Bossuyt et al. 1996 Dresser et al. 2002). Their role and substrate specificity are currently evaluated in detail. 

Masuda S,Takeuchi A, Saito El, ElashimotoY, Inui K. Functional analysis of rat renal organic anion transporter OAT-Kl bidirectional methotrexate transport in apical membrane. FEES Letters 1999 459 128-132. 

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