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- Title
Characterization of the transport of the organic cation [<sup>3</sup>H]MPP<sup>+</sup> in human intestinal epithelial (Caco-2) cells.
- Authors
Martel, F.; Calhau, C.; Azevedo, I.
- Abstract
The aim of this study was to characterize the transport of organic cations at the intestinal level, by studying the characteristics of the transport of 1-methyl-4-phenylpyridinium (MPP+) in Caco-2 cells. Transepithelial flux as well as cellular accumulation of [3H]MPP+ were quantitatively similar when substrate was applied from the basolateral or apical cell membrane. Verapamil (100 µM) and rhodamine123 (10 µM) significantly reduced [3H]MPP+ transepithelial flux in the apical-to-basolateral direction. When cells were grown on plastic supports, [3H]MPP+ was rapidly accumulated in the cells, both by saturable and nonsaturable mechanisms. The kinetic parameters of the saturable component were: Km: 449 µM and Vmax: 2249 pmol per mg protein and 5 min. Uptake of [3H]MPP+ was metabolic energy-dependent and Na+-, pH- and potential-independent. It was inhibited by several organic cations (verapamil, rhodamine123, daunomycin, vinblastine, tetrabutylammonium and vecuronium) but not by others (tetraethylammonium and N-methylnicotinamide). Decynium22 and corticosterone inhibited [3H]MPP+ uptake into the cells. The P-glycoprotein antibody UIC2 (20 µg/ml) had no effect. In conclusion, [3H]MPP+ is efficiently transported by Caco-2 cells in both basolateral-to-apical (secretion) and apical-to-basolateral (absorption) directions. Absorption of [3H]MPP+ at the apical membrane 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.
- Subjects
CELLULAR mechanics; ABSORPTION; CALCIUM antagonists; CARDIOVASCULAR agents; CELL membranes; P-glycoprotein
- Publication
Naunyn-Schmiedeberg's Archives of Pharmacology, 2000, Vol 361, Issue 5, p505
- ISSN
0028-1298
- Publication type
Article
- DOI
10.1007/s002100000223