Drug Metabolism and Pharmacokinetics
Online ISSN : 1880-0920
Print ISSN : 1347-4367
ISSN-L : 1347-4367
Carnitine precursor γ-butyrobetaine is a novel substrate of the Na+ and Cl-dependent GABA transporter Gat2
Takeo NakanishiYoko FukuyamaMasaharu FujitaYoshiyuki ShirasakaIkumi Tamai
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JOURNAL FREE ACCESS Advance online publication

Article ID: DMPK-11-NT-053

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Abstract

  To study transport of the carnitine precursor gamma-butyrobetaine (GBB) by rat liver-specific GABA transporter 2 (rGat2), we measured the uptake of deuterated GBB (d3-GBB) by Xenopus oocytes expressing rGat2. rGat2-mediated d3-GBB uptake was Na+ and Cl-dependent and saturable with Km of 70.6 ± 34.8 µM. In carnitine transporter Octn2-deficient Jvs mice, mRNA expression of mGat3, the mouse orthologue of GAT2, was decreased in liver, but increased in brain, while mRNA expression of mBbox1, which hydroxylates GBB to carnitine, increased in kidneys and brain. These results indicate that Gat2 plays a role in transmembrane transport of GBB.

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© 2011 by The Japanese Society for the Study of Xenobiotics
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