Document Detail

Mechanism of the inhibitory effect of zwitterionic drugs (levofloxacin and grepafloxacin) on carnitine transporter (OCTN2) in Caco-2 cells.
MedLine Citation:
PMID:  16928358     Owner:  NLM     Status:  MEDLINE    
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.
Takeshi Hirano; Satoru Yasuda; Yuki Osaka; Masaki Kobayashi; Shirou Itagaki; Ken Iseki
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Publication Detail:
Type:  Journal Article     Date:  2006-07-14
Journal Detail:
Title:  Biochimica et biophysica acta     Volume:  1758     ISSN:  0006-3002     ISO Abbreviation:  Biochim. Biophys. Acta     Publication Date:  2006 Nov 
Date Detail:
Created Date:  2006-11-07     Completed Date:  2007-01-03     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0217513     Medline TA:  Biochim Biophys Acta     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  1743-50     Citation Subset:  IM    
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
Biological Transport, Active / drug effects*,  physiology
Caco-2 Cells
Carnitine / metabolism*
Dose-Response Relationship, Drug
Fluoroquinolones / pharmacology*
Hydrogen-Ion Concentration
Intestines / cytology,  metabolism
Leucovorin / pharmacology*
Membrane Proteins / analysis,  metabolism*
Organic Cation Transport Proteins / antagonists & inhibitors*
Piperazines / pharmacology*
Reg. No./Substance:
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

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