Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
Evidence for overlapping substrate specificity between large neutral aminoacid (LNAA) and dipeptide (hPEPT1) transporters for PD 158473, an NMDA antagonist
Autore:
Surendran, N; Covitz, KMY; Han, HK; Sadee, W; Oh, DM; Amidon, GL; Williamson, RM; Bigge, CF; Stewart, BH;
Indirizzi:
WarnerDynamert Parke Davis, Parke Davis Pharmaceut Res, Dept PharmacokinetWarner Lambert Parke Davis Ann Arbor MI USA 48105 Res, Dept Pharmacokinet Univncisco,San Francisco, Dept Biopharmaceut Sci & Pharmaceut Chem, San Fra Univ Calif San Francisco San Francisco CA USA 94143 rmaceut Chem, San Fra Univ Michigan, Coll Pharm, Ann Arbor, MI 48109 USA Univ Michigan Ann Arbor MI USA 48109 Coll Pharm, Ann Arbor, MI 48109 USA Warnerr,ambert Parke Davis, Parke Davis Pharmaceut Res, Dept Chem, Ann Arbo Warner Lambert Parke Davis Ann Arbor MI USA 48105 es, Dept Chem, Ann Arbo WarnerArbor,rt Parke Davis, Parke Davis Pharmaceut Res, Dept Mol Biol, AnnWarner Lambert Parke Davis Ann Arbor MI USA 48105 Res, Dept Mol Biol, Ann
Titolo Testata:
PHARMACEUTICAL RESEARCH
fascicolo: 3, volume: 16, anno: 1999,
pagine: 391 - 395
SICI:
0724-8741(199903)16:3<391:EFOSSB>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
HAMSTER OVARY CELLS; OLIGOPEPTIDE TRANSPORTER; STRUCTURAL REQUIREMENTS; CACO-2 CELLS; SYSTEM; COTRANSPORT;
Keywords:
large neutral amino acid transporter; di/tripeptide transporter; CHO-PEPT1 cells; NMDA antagonist;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
15
Recensione:
Indirizzi per estratti:
Indirizzo: Surendran, N WarnerDynamert Parke Davis, Parke Davis Pharmaceut Res, Dept Pharmacokinet Warner Lambert Parke Davis Ann Arbor MI USA 48105 rmacokinet
Citazione:
N. Surendran et al., "Evidence for overlapping substrate specificity between large neutral aminoacid (LNAA) and dipeptide (hPEPT1) transporters for PD 158473, an NMDA antagonist", PHARM RES, 16(3), 1999, pp. 391-395

Abstract

Purpose. The objective of this research was to investigate the substrate specificity of large neutral amino acid carrier (LNAA) and di/tripeptide (hPEPT1) transporters with respect to PD 158473, an NMDA antagonist. Methods. Cellular uptake studies were carried out using two types of Chinese Hamster Ovary (CHO). CHO-KI cells represent the wild type with inherent large neutral amino acid (LNAA) activity. CHO-PEPT1 cells were generated bystable transfection of hPEPT1 gene into CHO cells. Therefore, these cells possess both LNAA activity and di/tripeptide transporter activities as a result of the transfection. Cellular uptake of PD 158473 was quantified usinga HPLC method previously developed in our laboratory. Results. The utility of the CHO-PEPT1 cell model was demonstrated by determining the uptake kinetics of Gly-Sar, a prototypical dipeptide transportersubstrate. Uptake kinetics of PD 158473 displayed two carrier-mediated transport components in CHO-PEPT1 cells, while in CHO-K I cells the relationship was consistent with classic one component Michaelis-Menten kinetics. These results confirmed the affinity of PD 158473 for both LNAA and di/tripeptide transporters. Further, results from inhibition experiments using these two cell types indicate that the high affinity-low capacity system was the LNAA carrier and the low affinity-high capacity carrier was the di/tripeptide transporter. Conclusions. This study demonstrates overlapping substrate specificity between LNAA carrier and di/tripeptide transporter (hPEPT1) for PD 158473, an amino acid analog. Establishing Structure Transport Relationship (STR) for this overlap will aid in a design strategy for increasing oral absorption or targeting specific drugs to selected tissues.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/07/20 alle ore 22:09:26