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

• Tipo: Artigo em Revista Científica Internacional
• Data: 1999

Autores

Martel, F (Autor) FMUP; ribeiro, l (Autor) Outra; Conceicao Calhau (Autor) FCNAUP; Azevedo, I (Autor) Outra

Revista

Título: European Journal of Pharmacology

Vol. 379

Páginas: 211-218

ISSN: 0014-2999

Editora: Elsevier

Indexação

ISI Web of Knowledge - 9 Citações

Scopus - 9 Citações

Outras Informações

ID Authenticus: 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+.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 8