Transport of small organic cations in the rat liver - The role of the organic cation transporter OCT1

• Type: Article in International Scientific Journal
• Date: 1996

Authors

Martel, F (Author) FMUP; Vetter, T (Author) Other; Russ, H (Author) Other; Grundemann, D (Author) Other; Azevedo, I (Author) Other; Koepsell, H (Author) Other; Schomig, E (Author) Other

Journal

Title: Naunyn-Schmiedeberg's Archives of Pharmacology

Vol. 354

Pages: 320-326

ISSN: 0028-1298

Publisher: Springer Nature

Indexing

ISI Web of Knowledge - 84 Citations

Scopus - 89 Citations

Other information

Authenticus ID: P-001-DYW

Abstract (EN): 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 7