期刊
NAUNYN-SCHMIEDEBERGS ARCHIVES OF PHARMACOLOGY
卷 363, 期 1, 页码 1-10出版社
SPRINGER-VERLAG
DOI: 10.1007/s002100000302
关键词
brain capillary endothelial cells; MPP+; transport; amphiphilic solute facilitator family
The aim of this study was to characterize the transport of the organic cation 1-methyl-4-phenylpyridinium (MPP+) in an immortalized cell line of rat capillary cerebral endothelial cells (RBE 4). Verapamil (100 muM) and rhodamine123 (10 muM), and decynium22 (2 muM) and corticosterone (100 muM) reduced cellular accumulation of [H-3]MPP+ applied from the luminal and abluminal cell border, respectively. When cells were grown on plastic supports, [H-3]MPP+ accumulated in the cells. The kinetic parameters of the saturable component were: K-m = 25 muM and V-max = 246 pmol per mg protein and 15 min. A selective organic anion transport inhibitor and selective inhibitors of the L- and A-type amino acid transporters did not affect [H-3]MPP+ uptake. Uptake of [H-3]MPP+ was Na+-independent and metabolic energy-, pH- and potential-dependent. It was inhibited by several organic cations (e.g., verapamil, quinidine, daunomycin, dopamine) but not by others (cimetidine, tetraethylammonium, N-methylnicotinamide). In conclusion, [H-3]MPP+ is efficiently transported by RBE 4 cells in both abluminal-to-luminal and luminal-to-abluminal directions. Absorption of [H-3]MPP+ seems to occur through a carrier-mediated mechanism belonging to the amphiphilic solute facilitator (ASF) family of transporters, but distinct from the known members of this family.
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