Characterization of the efflux of the organic cation MPP+ in cultured rat hepatocytes

• Type: Article in International Scientific Journal
• Date: 1999

Authors

Martel, F (Author) FMUP; ribeiro, l (Author) Other; Conceicao Calhau (Author) FCNAUP; Azevedo, I (Author) Other

Journal

Title: European Journal of Pharmacology

Vol. 379

Pages: 211-218

ISSN: 0014-2999

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 9 Citations

Scopus - 9 Citations

Other information

Authenticus ID: P-001-3M3

DOI: 10.1016/s0014-2999(99)00501-4

Abstract (EN): The aim of this study was to characterize the efflux of organic cations from primary cultured rat hepatocytes, using 1-methyl-4-phenylpyridinium (MPP+) as a model compound. The efflux of [H-3]MPP+ was temperature dependent, and pH and metabolic inhibition independent. It was either strongly reduced (verapamil, vinblastine and rhodamine123) or only moderately reduced (daunomycin) by other organic cations. The anti-P-glycoprotein antibody UIC2 (20 mu g/ml) and the P-glycoprotein inhibitors vanadate and cyclosporine A had no effect on [H-3]MPP+ efflux. Decynium22 and corticosterone, known inhibitors of rat Organic Cation Transporter 1 (rOCT1), markedly reduced [H-3]MPP+ efflux. The uptake of [H-3]MPP+ into hepatocytes, known to be mediated by rOCT1, was inhibited by verapamil and vinblastine (IC(50)s of 2.6 and 34.4 mu M, respectively). In conclusion, [H-3]MPP+ efflux from primary cultured rat hepatocytes appears to be mediated by rOCT1, a polyspecific organic cation transporter. Moreover, our results do not support the involvement of P-glycoprotein or of an organic cation/proton antiporter in the efflux of [H-3]MPP+.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 8