Effect of P-glycoprotein modulators on the human extraneuronal monoamine transporter

• Type: Article in International Scientific Journal
• Date: 2001

Authors

Martel, F (Author) FMUP; Elisa Keating (Author) FMUP; Azevedo, I (Author) Other

Journal

Title: European Journal of Pharmacology

Vol. 422

Pages: 31-37

ISSN: 0014-2999

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 7 Citations

Scopus - 7 Citations

Other information

Authenticus ID: P-000-V6A

DOI: 10.1016/s0014-2999(01)01055-x

Abstract (EN): The aim of this work was to investigate the effect of P-glycoprotein modulators on human extraneuronal monoamine transporter (EMT)-mediated transport. The experiments were performed using a cell line From human embryonic kidney (HEK293 cells) stably transfected with pcDNA3hEMT (293(hEMT)), or with pcDNA3 alone (293(control)). Of the P-glycoprotein modulators tested, rhodamine123. verapamil and daunomycin concentration-dependently inhibited EMT-mediated uptake of [H-3]1-methyl-4-phenylpyridinium ([H-3]MPP+). The corresponding IC50's were found to be 3.6, 37 and 130 muM, respectively. By contrast, vinblastine, digitoxin and cyclosporine A were devoid of effect. The endogenous organic cation tyramine, but not choline, inhibited EMT-mediated transport (IC50 of 468 muM). Moreover, L-arginine and L-histidine (up to 1 mM) did not affect [H-3]MPP+ uptake. Finally, MPP+ and tyramine trans-stimulated [H-3]MPP+ uptake, but rhodamine 123 had no effect, and verapamil and daunomycin trans-inhibited [H-3]MPP+ uptake. In conclusion, this study shows that several cationic modulators of P-glycoprotein inhibit EMT-mediated transport. As a consequence, the interaction of P-glycoprotein modulators with EMT must be taken into account, and the consequences of this interaction must not be forgotten when using such drugs in vivo.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 7