Hiroki Tsuchida, Naohiko Anzai, Ho J Shin, Michael F Wempe, Promsuk Jutabha, Atsushi Enomoto, Seok H Cha, Takeo Satoh, Masashi Ishida, Hiroyuki Sakurai, Hitoshi Endou
Department of Pharmacology and Toxicology, Kyorin University School of Medicine, Tokyo, Japan.
Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 2010This study identifies a novel organic anion transporter Oat9 expressed in mouse liver and kidney. Two variants were detected by screening a mouse liver cDNA library; these varients consist of 1815 (designated Oat9S) and 2165 (Oat9L) base pairs which encode 443 and 551 amino acid proteins, respectively. Oat9S has a predicted structure containing eight transmembrane domains (TMD); whereas, Oat9L possesses twelve TMD. Oat9 mRNA expression was detected in kidney and liver. This transporter was located at the apical side of the late portion of proximal tubules and at the sinusoidal side of hepatocytes. When expressed in Xenopus oocytes, Oat9S mediated the transport of L-carnitine (Km = 2.9 microM), a representative zwitterion, as well as cimetidine (Km = 16.1 microM) and salicylic acid (Km = 175.5 microM), while Oat9L did not show any transport activity. Oat9S-mediated L-carnitine uptake was inhibited by D-carnitine, acetylcarnitine, octanoylcarnitine, betaine, and other organic compounds, suggesting that quaternary ammonium cation bulkiness and relative hydrophobicity are important factors for Oat9S-substrate interactions. Among OATs, Oat9S appears to be the first member to mediate the transport of carnitine and possesses eight TMD. Overall, these new results provide added insight into the structure-activity relationship comprising the organic ion-permeation pathway. 2010 S. Karger AG, Basel.
Hiroki Tsuchida, Naohiko Anzai, Ho J Shin, Michael F Wempe, Promsuk Jutabha, Atsushi Enomoto, Seok H Cha, Takeo Satoh, Masashi Ishida, Hiroyuki Sakurai, Hitoshi Endou. Identification of a novel organic anion transporter mediating carnitine transport in mouse liver and kidney. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology. 2010;25(4-5):511-22
PMID: 20332632
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