Martel, F. and Vetter, T. and Russ, Hermann and Gründemann, D. and Azevedo, I. and Koepsell, H. and Schömig, E. (1996) Transport of small organic cations in the rat liver - The role of the organic cation transporter OCT1. NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY, 354 (3). pp. 320-326. ISSN 0028-1298, 1432-1912
Full text not available from this repository.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 the small organic cation H-3-1-methyl-4-phenylpyridinium (H-3-MPP(+)). At equilibrium, 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 results indicate 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 I substrates.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | CARRIER-MEDIATED TRANSPORT; EXTRANEURONAL NORADRENALINE TRANSPORT; BASOLATERAL MEMBRANE-VESICLES; RENAL BRUSH-BORDER; HEPATIC-UPTAKE; BILIARY-EXCRETION; TETRAETHYLAMMONIUM; HEPATOCYTES; SYSTEMS; CELLS; rat liver; transport of organic cations; OCT1; type I hepatic transport of cationic drugs; 1-methyl-4-phenylpyridinium |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Psychiatrie und Psychotherapie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 02 Nov 2023 05:41 |
| Last Modified: | 02 Nov 2023 05:41 |
| URI: | https://pred.uni-regensburg.de/id/eprint/51580 |
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