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Titolo:
SUBSTRATE-SPECIFICITY OF THE DI TRIPEPTIDE TRANSPORTER IN HUMAN INTESTINAL EPITHELIA (CACO-2) - IDENTIFICATION OF SUBSTRATES THAT UNDERGO H+-COUPLED ABSORPTION/
Autore:
THWAITES DT; HIRST BH; SIMMONS NL;
Indirizzi:
MED SCH NEWCASTLE UPON TYNE,SCH MED,GASTROINTESTINAL DRUT DELIVERY RES CTR,DEPT PHYSIOL SCI NEWCASTLE TYNE NE2 4HH TYNE & WEAR ENGLAND
Titolo Testata:
British Journal of Pharmacology
fascicolo: 3, volume: 113, anno: 1994,
pagine: 1050 - 1056
SICI:
0007-1188(1994)113:3<1050:SOTDTT>2.0.ZU;2-1
Fonte:
ISI
Lingua:
ENG
Soggetto:
BRUSH-BORDER MEMBRANE; DIPEPTIDE GLYCYLSARCOSINE TRANSPORT; CELL LINE CACO-2; BASOLATERAL MEMBRANES; HORMONE TRH; MONOLAYERS; VESICLES; AMINOCEPHALOSPORINS; GRADIENT; JEJUNUM;
Keywords:
PROTON-COUPLED TRANSPORT; DIPEPTIDE; INTESTINE; EPITHELIUM; CACO-2 CELLS; CELL CULTURE; CEPHALOSPORIN; INTRACELLULAR PH;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
35
Recensione:
Indirizzi per estratti:
Citazione:
D.T. Thwaites et al., "SUBSTRATE-SPECIFICITY OF THE DI TRIPEPTIDE TRANSPORTER IN HUMAN INTESTINAL EPITHELIA (CACO-2) - IDENTIFICATION OF SUBSTRATES THAT UNDERGO H+-COUPLED ABSORPTION/", British Journal of Pharmacology, 113(3), 1994, pp. 1050-1056

Abstract

1 pH-dependent transepithelial transport and intracellular accumulation of the hydrolysis-resistant dipeptide glycylsarcosine (Gly-Sar) have been demonstrated in the model human intestinal epithelial cell line, Caco-2. 2 Experiments with BCECF is(2-carboxyethyl)-5(6)-carboxyfluorescein)-loaded Caco-2 cells demonstrated that dipeptide (Gly-Sar) transport across the apical membrane is coupled to proton flow into the cell. 3 A range of postulated substrates for the intestinal di/tripeptide carrier were tested for their abilities to: (a) inhibit pH-dependent [C-14]Gly-Sar apical-to-basal transport and intracellular accumulation and (b) stimulate H+ flow across the apical surface of BCECF-loadedCaco-2 cell monolayers. 4 A range of compounds (including Gly-Gly, Leu-Leu, Gly-Gly-Gly, cefadroxil and cephalexin) caused marked acidification of intracellular pH when perfused at the apical surface of Caco-2cell monolayers. In contrast leucine and D-Leu-D-Leu failed to induceproton flow. The ability to induce proton-flow across the apical surface by these compounds, in this intestinal epithelium, was directly correlated to the relative inhibitory effects on [C-14]-Gly-Sar transport and accumulation. 5 The determination of substrate-induced intracellular pH change in the Caco-2 cell system may provide a useful rapid screen for candidate substrates for absorption via H+-coupled transport mechanisms such as the intestinal di/tripeptide carrier in an appropriate physiological context.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 30/03/20 alle ore 08:53:47