| Interaction and transport of kynurenic acid via human organic anion transporters hOAT1 and hOAT3. | |
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MedLine Citation:
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PMID: 22108572 Owner: NLM Status: Publisher |
Abstract/OtherAbstract:
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Kynurenic acid, a catabolite of tryptophan, is suggested to be involved in schizophrenia, and is known to be a uremic toxin, although there is little information about the mechanism of its disposition. In this study, we performed uptake experiment using Xenopus laevis oocyte expression system to examine the transport of kynurenic acid by human organic anion transporters hOAT1 (SLC22A6) and hOAT3 (SLC22A8), which mediate the transport of organic anions in the brain and kidney. The uptake of p-aminohippurate in hOAT1-expressing oocytes and of estrone sulfate in hOAT3-expressing oocytes was strongly inhibited by kynurenic acid, and other tryptophan catabolites, kynurenine and quinolinic acid, showed moderate and no inhibition, respectively. The apparent 50% inhibitory concentrations of kynurenic acid were estimated to be 12.9μM for hOAT1, and 7.76μM for hOAT3. Both hOAT1 and hOAT3 markedly stimulated the uptake of kynurenic acid into oocytes, and the K(m) values of the transport were calculated to be 5.06μM and 4.86μM, respectively. The transport efficiencies of kynurenic acid by hOAT1 and hOAT3 were comparable to those of p-aminohippurate and estrone sulfate, respectively. Probenecid inhibited kynurenic acid transport by hOAT1 and hOAT3. These findings show the interaction of kynurenic acid with hOAT1 and hOAT3, and that kynurenic acid is their substrate. It is suggested that these transporters are involved in the disposition of kynurenic acid. |
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Authors:
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Yuichi Uwai; Hiroaki Honjo; Kikuo Iwamoto |
Publication Detail:
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Type: JOURNAL ARTICLE Date: 2011-11-16 |
Journal Detail:
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Title: Pharmacological research : the official journal of the Italian Pharmacological Society Volume: - ISSN: 1096-1186 ISO Abbreviation: - Publication Date: 2011 Nov |
Date Detail:
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Created Date: 2011-11-23 Completed Date: - Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 8907422 Medline TA: Pharmacol Res Country: - |
Other Details:
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Languages: ENG Pagination: - Citation Subset: - |
Copyright Information:
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Copyright © 2011 Elsevier Ltd. All rights reserved. |
Affiliation:
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Laboratory of Clinical Pharmacodynamics, School of Pharmacy, Aichi Gakuin University, 1-100, Kusumoto-cho, Chikusa-ku, Nagoya-shi 464-8650, Japan. |
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From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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