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Titolo:
Carnitine transport acid its inhibition by sulfonylureas in human kidney proximal tubular epithelial cells
Autore:
Huang, W; Shaikh, SN; Ganapathy, ME; Hopfer, U; Leibach, FH; Carter, AL; Ganapathy, V;
Indirizzi:
Med Coll Georgia, Dept Biochem & Mol Biol, Augusta, GA 30912 USA Med Coll Georgia Augusta GA USA 30912 m & Mol Biol, Augusta, GA 30912 USA Med Coll Georgia, Dept Med, Augusta, GA 30912 USA Med Coll Georgia Augusta GA USA 30912 ia, Dept Med, Augusta, GA 30912 USA Case Western Reserve Univ, Dept Physiol & Biophys, Cleveland, OH 44106 USACase Western Reserve Univ Cleveland OH USA 44106 Cleveland, OH 44106 USA
Titolo Testata:
BIOCHEMICAL PHARMACOLOGY
fascicolo: 8, volume: 58, anno: 1999,
pagine: 1361 - 1370
SICI:
0006-2952(19991015)58:8<1361:CTAIIB>2.0.ZU;2-#
Fonte:
ISI
Lingua:
ENG
Soggetto:
ORGANIC CATION TRANSPORTER; BRUSH-BORDER MEMBRANE; DIETARY CARNITINE; CLONING; DEFICIENCY; RECEPTOR; CARDIOMYOPATHY; VESICLES; DISEASE; CHANNEL;
Keywords:
humans; proximal tubular cell; renal absorption; carnitine uptake; carnitine acyl eaters; sulfonylureas;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
35
Recensione:
Indirizzi per estratti:
Indirizzo: Ganapathy, V Med Coll Georgia, Dept Biochem & Mol Biol, Augusta, GA 30912 USA Med Coll Georgia Augusta GA USA 30912 Augusta, GA 30912 USA
Citazione:
W. Huang et al., "Carnitine transport acid its inhibition by sulfonylureas in human kidney proximal tubular epithelial cells", BIOCH PHARM, 58(8), 1999, pp. 1361-1370

Abstract

The kidney plays an important role in the homeostasis of carnitine by its ability to reabsorb carnitine almost completely from the glomerular filtrate. The transport process responsible for this reabsorption has been investigated thus far only in laboratory animals. Here we report on the characteristics of carnitine uptake in a proximal tubular epithelial cell line derived from human kidney. The uptake process was found to be obligatorily dependent on Na+ with no involvement of anions. The process was saturable, with aMichaelis-Menten constant of 14 +/- 1 mu M. The Na+:carnitine stoichiometry was 1:1. The same process also was found to be responsible for the uptakeof acetylcarnitine and propionylcarnitine, two acyl esters of carnitine with potential for therapeutic use in humans. The uptake process was specificfor carnitine and its acyl esters. Betaine, a structural analog of carnitine, interacted with the uptake process to a significant extent. The presentstudies also showed that sulfonylureas, oral hypoglycemic agents currentlyused in the management of type 2 diabetes, inhibited the carnitine uptake system. Among the sulfonylureas tested, glibenclamide was the most potent inhibitor. The inhibition was competitive. Glibenclamide inhibited the uptake not only of carnitine but also of acetylcarnitine and propionylcarnitine. The inhibition most likely was the result of direst interaction of the compound with the carnitine transporter because the inhibition could be demonstrated in purified rat kidney brush border membrane vesicles. (C) 1999 Elsevier Science Inc.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 11/07/20 alle ore 21:09:13