| Mechanism of the inhibitory effect of zwitterionic drugs (levofloxacin and grepafloxacin) on carnitine transporter (OCTN2) in Caco-2 cells. | |
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MedLine Citation:
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PMID: 16928358 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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L-Carnitine plays an important role in lipid metabolism by facilitating the transport of long-chain fatty acids across the mitochondrial inner membrane followed by fatty acid beta-oxidation. It is known that L-carnitine exists as a zwitterion and that member of the OCTN family play an important role in its transport. The aims of this study were to characterize L-carnitine transport in the intestine by using Caco-2 cells and to elucidate the effects of levofloxacin (LVFX) and grepafloxacin (GPFX), which are zwitterionic drugs, on L-carnitine uptake. Kinetic analysis showed that the half-saturation Na+ concentration, Hill coefficient and Km value of L-carnitine uptake in Caco-2 cells were 10.3 +/- 4.5 mM, 1.09 and 8.0 +/- 1.0 microM, respectively, suggesting that OCTN2 mainly transports L-carnitine. LVFX and GPFX have two pKa values and the existence ratio of their zwitterionic forms is higher under a neutral condition than under an acidic condition. Experiments on the inhibitory effect of LVFX and GPFX on L-carnitine uptake showed that LVFX and GPFX inhibited L-carnitine uptake more strongly at pH 7.4 than at pH 5.5. It was concluded that the zwitterionic form of drugs plays an important role in inhibition of OCTN2 function. |
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Authors:
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Takeshi Hirano; Satoru Yasuda; Yuki Osaka; Masaki Kobayashi; Shirou Itagaki; Ken Iseki |
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Publication Detail:
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Type: Journal Article Date: 2006-07-14 |
Journal Detail:
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Title: Biochimica et biophysica acta Volume: 1758 ISSN: 0006-3002 ISO Abbreviation: Biochim. Biophys. Acta Publication Date: 2006 Nov |
Date Detail:
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Created Date: 2006-11-07 Completed Date: 2007-01-03 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0217513 Medline TA: Biochim Biophys Acta Country: Netherlands |
Other Details:
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Languages: eng Pagination: 1743-50 Citation Subset: IM |
Affiliation:
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Department of Clinical Pharmaceutics and Therapeutics, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita-12-jo, Nishi-6-chome, Kita-ku, Sapporo 060-0812, Japan. |
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| MeSH Terms | |
Descriptor/Qualifier:
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Biological Transport, Active
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drug effects*,
physiology Caco-2 Cells Carnitine / metabolism* Dose-Response Relationship, Drug Fluoroquinolones / pharmacology* Humans Hydrogen-Ion Concentration Intestines / cytology, metabolism Kinetics Leucovorin / pharmacology* Membrane Proteins / analysis, metabolism* Organic Cation Transport Proteins / antagonists & inhibitors* Piperazines / pharmacology* |
| Chemical | |
Reg. No./Substance:
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0/Fluoroquinolones; 0/Membrane Proteins; 0/Organic Cation Transport Proteins; 0/Piperazines; 0/SLC22A5 protein, human; 119914-60-2/grepafloxacin; 541-15-1/Carnitine; 58-05-9/Leucovorin |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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