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Titolo:
A human lymphocyte based ex vivo assay to study the effect of drugs on P-glycoprotein (P-gp) function
Autore:
Parasrampuria, DA; Lantz, MV; Benet, LZ;
Indirizzi:
Univ Calif San Francisco, Sch Pharm, Dept Biopharmaceut Sci, San Francisco, CA 94143 USA Univ Calif San Francisco San Francisco CA USA 94143 ancisco, CA 94143 USA Univ Calif San Francisco, Sch Med, Dept Surg, San Francisco, CA 94143 USA Univ Calif San Francisco San Francisco CA USA 94143 ancisco, CA 94143 USA
Titolo Testata:
PHARMACEUTICAL RESEARCH
fascicolo: 1, volume: 18, anno: 2001,
pagine: 39 - 44
SICI:
0724-8741(200101)18:1<39:AHLBEV>2.0.ZU;2-U
Fonte:
ISI
Lingua:
ENG
Soggetto:
MULTIDRUG-RESISTANCE; CACO-2 MONOLAYERS; EFFLUX PUMP; CELL-LINE; TRANSPORT; GENE; OVEREXPRESSION; EXPRESSION; SECRETION; REVERSAL;
Keywords:
P-glycoprotein (P-gp); multidrug resistance associated protein (MRP); rhodamine 123; flow cytometer; cyclosporine; tacrolimus; vinblastine; verapamil; quinidine;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
24
Recensione:
Indirizzi per estratti:
Indirizzo: Benet, LZ Univ Calif San Francisco, Sch Pharm, Dept Biopharmaceut Sci, SanFrancisco, CA 94143 USA Univ Calif San Francisco San Francisco CA USA 94143 A 94143 USA
Citazione:
D.A. Parasrampuria et al., "A human lymphocyte based ex vivo assay to study the effect of drugs on P-glycoprotein (P-gp) function", PHARM RES, 18(1), 2001, pp. 39-44

Abstract

Purpose. The effect of drugs on P-glycoprotein (P-gp) is normally studied in transfected or overexpressing cell lines derived from tumor cells or animal tissue. We wanted to develop an assay using normal healthy human tissueto study and characterize the drug-transporter interaction. Methods. Lymphocytes were isolated from healthy human blood. The effect ofinhibitors of P-gp (cyclosporine, tacrolimus, verapamil, quinidine, vinblastine) and of other transporters (indomethacin, probenecid, sulfinpyrazone)on intracellular accumulation of rhodamine 123 was evaluated by flow cytometry. Results. The efflux of rhodamine 123 was inhibited by P-gp inhibitors in asaturable, concentration-dependent manner. The potency of inhibition of P-gp was cyclosporine > tacrolimus > quinidine > verapamil > vinblastine. Vinblastine inhibited P-gp at lower concentrations, whereas at high concentrations, there was an activation of rhodamine 123 efflux from lymphocytes. Themultidrug resistance associated protein (MRP) inhibitors, sulfinpyrazone and probenecid, did not have any significant effect on intracellular accumulation of rhodamine 123, but indomethacin caused a concentration-dependent increase in retention of rhodamine 123, indicating the involvement of other uncharacterized transporters. Conclusions. Lymphocytes can serve as a model tissue for studying modulation of P-gp activity by drugs. Both inhibitors and inducers of P-gp activitycan be evaluated.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 07/07/20 alle ore 21:11:06