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Titolo:
MOLECULAR AND CELL BIOLOGICAL ANALYSES FO R INTESTINAL-ABSORPTION ANDRENAL EXCRETION OF DRUGS
Autore:
SAITO H;
Indirizzi:
KYOTO UNIV HOSP,DEPT PHARM,SAKYO KU KYOTO 60601 JAPAN
Titolo Testata:
Yakugaku zasshi
fascicolo: 8, volume: 117, anno: 1997,
pagine: 522 - 541
SICI:
0031-6903(1997)117:8<522:MACBAF>2.0.ZU;2-7
Fonte:
ISI
Lingua:
JPN
Soggetto:
BRUSH-BORDER MEMBRANES; ORGANIC CATION-TRANSPORT; GRADIENT-DEPENDENT TRANSPORT; RAT H+/PEPTIDE COTRANSPORTER; CARRIER-MEDIATED TRANSPORT; BASOLATERAL MEMBRANES; EXPRESSION CLONING; LINE CACO-2; TRANSCELLULAR TRANSPORT; FUNCTIONAL EXPRESSION;
Keywords:
DRUG TRANSPORT; INTESTINAL ABSORPTION; RENAL TUBULAR SECRETION; PEPTIDE TRANSPORTER; BETA-LACTAM ANTIBIOTICS; ORGANIC ANION;
Tipo documento:
Review
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
43
Recensione:
Indirizzi per estratti:
Citazione:
H. Saito, "MOLECULAR AND CELL BIOLOGICAL ANALYSES FO R INTESTINAL-ABSORPTION ANDRENAL EXCRETION OF DRUGS", Yakugaku zasshi, 117(8), 1997, pp. 522-541

Abstract

Intestinal absorption and renal tubular secretion are transport processes determining the availability and the disposition of drugs in the body. In this review, our studies on the molecular and cell biologicalanalyses of intestinal absorption and renal secretion of drugs are described. We evaluated the transepithelial transport and the cellular accumulation of peptide-like drugs such as beta-lactam antibiotics and bestatin (a dipeptide-like antineoplastic agent) in the human adenocarcinoma colon cell line, Caco-2, as an in vitro model for studying absorption mechanisms of these drugs. We have found that the transcellulartransport of these peptide-like drugs is mediated by both the apically-and basolaterally-localized peptide transporters. To characterize molecular aspects of absorption of the peptide-like drugs, we studied cDNA cloning of H+/peptide cotransporters, PEPT1 and PEPT2, expressed inrats. The rat PEPT1 has been shown to mediate the H+-coupled uphill transport of beta-lactam antibiotics across the brush-border membranes of the intestinal and renal epithelia. The rat PEPT2 is expressed predominantly in the kidney, but not in the intestine, mediating tubular reabsorption of the peptide-like drugs. We examined the transcellular transport of organic cations across monolayers of the kidney epithelialcell line, LLC-PK1. We have found that LLC-PK1 cells possess the H+/organic cation antiporter and the membrane potential-sensitive organic cation transporter in the apical and basolateral membranes, respectively, thereby tetraethylammonium (TEA) being transported unidirectionally from the basolateral to the apical side of the monolayers. We have isolated a cDNA encoding a rat kidney-specific organic cation transporter, OCT 2, which transports TEA in a H+-gradient independent manner, suggesting that OCT2 is localized to the basolateral membranes of renaltubular cells. In addition, a cDNA encoding a novel rat organic aniontransporter, OAT-KI, has been cloned. OAT-K1 is expressed exclusivelyin the renal proximal tubules, and mediates the transport of methotrexate. Analyses of the molecular and cell biological mechanisms for drug absorption and secretion will provide information for the understanding of organ-specific drug transport systems and for the development of drug design and/or drug delivery system.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 01/04/20 alle ore 11:18:48