Catalogo Articoli (Spogli Riviste)

OPAC HELP

Titolo:
TRANSPORT OF SMALL ORGANIC CATIONS IN THE RAT-LIVER - THE ROLE OF THEORGANIC CATION TRANSPORTER OCT1
Autore:
MARTEL F; VETTER T; RUSS H; GRUNDEMANN D; AZEVEDO I; KOEPSELL H; SCHOMIG E;
Indirizzi:
UNIV HEIDELBERG,DEPT PHARMACOL,NEUENHEIMER FELD 366 D-69120 HEIDELBERG GERMANY UNIV HEIDELBERG,DEPT PHARMACOL D-69120 HEIDELBERG GERMANY FAC MED PORTO,INST PHARMACOL & THERAPEUT P-4200 OPORTO PORTUGAL UNIV REGENSBURG,DEPT NEUROL & PSYCHIAT D-93042 REGENSBURG GERMANY UNIV WURZBURG,DEPT ANAT D-97070 WURZBURG GERMANY
Titolo Testata:
Naunyn-Schmiedeberg's archives of pharmacology
fascicolo: 3, volume: 354, anno: 1996,
pagine: 320 - 326
SICI:
0028-1298(1996)354:3<320:TOSOCI>2.0.ZU;2-0
Fonte:
ISI
Lingua:
ENG
Soggetto:
CARRIER-MEDIATED TRANSPORT; EXTRANEURONAL NORADRENALINE TRANSPORT; BASOLATERAL MEMBRANE-VESICLES; RENAL BRUSH-BORDER; HEPATIC-UPTAKE; BILIARY-EXCRETION; TETRAETHYLAMMONIUM; HEPATOCYTES; SYSTEMS; CELLS;
Keywords:
RAT LIVER; TRANSPORT OF ORGANIC CATIONS; OCT1; TYPE I HEPATIC TRANSPORT OF CATIONIC DRUGS; 1-METHYL-4-PHENYLPYRIDINIUM;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
35
Recensione:
Indirizzi per estratti:
Citazione:
F. Martel et al., "TRANSPORT OF SMALL ORGANIC CATIONS IN THE RAT-LIVER - THE ROLE OF THEORGANIC CATION TRANSPORTER OCT1", Naunyn-Schmiedeberg's archives of pharmacology, 354(3), 1996, pp. 320-326

Abstract

The kidneys and the liver are the principal organs for the inactivation of circulating organic cations. Recently, an organic cation transporter (OCT1) has been cloned from rat kidney. In order to answer the question whether OCT1 is involved also in hepatic uptake of organic cations, the pharmacological characteristics of organic cation transport in hepatocytes were compared to the characteristics of transiently expressed OCT1. Primary cultures of rat hepatocytes avidly accumulated thesmall organic cation H-3-1-methyl-4-phenylpyridinium (H-3-MPP(+)). Atequilibrium, the hepatocytes accumulated H-3-MPP(+) 56-fold. Initial rates of specific H-3-MPP(+) transport in hepatocytes were saturable. The half-saturating concentration was 13 mu mol/l. H-3-MPP(+) transport was sensitive to quinine (K-i = 0.79 mu mol/l) and cyanine863 (K-i =0.097 mu mol/l). Quinine and cyanine863 are known inhibitors of type I hepatic transport of cationic drugs and of renal excretion of organic cations, respectively. To compare the functional characteristics of H-3-MPP(+) transport in hepatocytes with those of OCT1, OCT1 has been heterologously expressed and characterized in a mammalian cell line (293 cells). Initial rates of H-3-MPP(+) transport were saturable, the K-m being 13 mu mol/l. The rank order of inhibitory potencies of various inhibitors was almost identical in hepatocytes and 293 cells transiently transfected with OCT1. There was a positive correlation between the K-i's for the inhibition of H-3-MPP(+) transport in isolated hepatocytes and transfected 293 cells (r = 0.85; P<0.01; n = 8). The resultsindicate that OCT1 is functionally expressed not only in the kidney but also in hepatocytes where it is responsible for the transport of small organic cations which, in the past, have been classified as type Isubstrates.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 12/07/20 alle ore 03:20:51