| Cl- -dependent upregulation of human organic anion transporters: different effects on transport kinetics between hOAT1 and hOAT3. | |
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MedLine Citation:
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PMID: 17429031 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Chloride ion has a stimulatory effect on the transport of organic anions across renal basolateral membranes. However, the exact mechanisms at molecular levels have been unclear as of yet. Human organic anion transporters hOAT1 and hOAT3 play important roles in renal basolateral membranes. In this study, the effects of Cl(-) on the activities of these transporters were evaluated by using HEK293 cells stably expressing hOAT1 or hOAT3 (HEK-hOAT1 or HEK-hOAT3). The uptake of p-[(14)C]aminohippurate by HEK-hOAT1 and [(3)H]estrone sulfate by HEK-hOAT3 was greater in the presence of Cl(-) than in the presence of SO(4)(2-) or gluconate. Additionally, the uptake of various compounds by HEK-hOAT1 and HEK-hOAT3 was significantly higher in the Cl(-)-containing medium than the gluconate-containing medium, suggesting that the influences of Cl(-) are not dependent on substrate and that Cl(-) directly stimulates the functions of hOAT1 and hOAT3. The substitution of gluconate with Cl(-) did not change the K(m) value for the uptake of p-[(14)C]aminohippurate by HEK-hOAT1 but caused an approximately threefold increase in the maximal uptake rate (V(max)) value. On the other hand, replacement of gluconate with Cl(-) decreased the K(m) value for the uptake of [(3)H]estrone sulfate and cefotiam by HEK-hOAT3 to about one-third, while it did not change the V(max) value. In summary, Cl(-) upregulates the activities of both hOAT1 and hOAT3, but its effects on transport kinetics differ between these transporters. It was suggested that Cl(-) participates in the trans-location process for hOAT1, and the substrate recognition process for hOAT3. |
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Authors:
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Harumasa Ueo; Hideyuki Motohashi; Toshiya Katsura; Ken-ichi Inui |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2007-04-11 |
Journal Detail:
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Title: American journal of physiology. Renal physiology Volume: 293 ISSN: 1931-857X ISO Abbreviation: Am. J. Physiol. Renal Physiol. Publication Date: 2007 Jul |
Date Detail:
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Created Date: 2007-07-09 Completed Date: 2007-08-17 Revised Date: 2011-04-28 |
Medline Journal Info:
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Nlm Unique ID: 100901990 Medline TA: Am J Physiol Renal Physiol Country: United States |
Other Details:
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Languages: eng Pagination: F391-7 Citation Subset: IM |
Affiliation:
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Department of Pharmacy, Kyoto University Hospital, Sakyo-ku, Kyoto 606-8507, Japan. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Cefotiam
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metabolism Cell Line Cell Membrane / drug effects, metabolism Chlorides / pharmacology* Estrone / analogs & derivatives, metabolism Gluconates / pharmacology Humans Ketoglutaric Acids / metabolism Kinetics Organic Anion Transport Protein 1 / biosynthesis, genetics, metabolism* Organic Anion Transporters, Sodium-Independent / biosynthesis, genetics, metabolism* Stimulation, Chemical Sulfates / metabolism Up-Regulation / physiology p-Aminohippuric Acid / metabolism |
| Chemical | |
Reg. No./Substance:
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0/Chlorides; 0/Gluconates; 0/Ketoglutaric Acids; 0/Organic Anion Transport Protein 1; 0/Organic Anion Transporters, Sodium-Independent; 0/Sulfates; 0/organic anion transport protein 3; 328-50-7/alpha-ketoglutaric acid; 481-97-0/estrone sulfate; 526-95-4/gluconic acid; 53-16-7/Estrone; 61-78-9/p-Aminohippuric Acid; 61622-34-2/Cefotiam |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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