Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.6.3.44 (P-glycoprotein)
 13,344 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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 microM) and rhodamine123 (10 microM) 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 microM and Vmax: 2,249 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 microg/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.
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PMID:Characterization of the transport of the organic cation [3H]MPP+ in human intestinal epithelial (Caco-2) cells. 1083 4

The objective of the current investigation was to examine the transport characteristics of choline, an endogenous quaternary ammonium compound, into human intestinal Caco-2 cells; the transport of choline has not been characterized in human intestine. The cellular accumulation of choline was independent of an inwardly directed Na(+) gradient and demonstrated temperature dependence and saturability. Using the initial uptake rates, choline accumulation was best characterized by a Michaelis-Menten equation and a diffusion component with a K(m) and V(max) of 110 +/- 3 micro mol/L and 2800 +/- 250 pmol/(mg protein. 10 min), respectively. Choline uptake was significantly inhibited by an excess of choline itself and by hemicholinium-3, a structural analog of choline. However other hydrophilic organic cations, such as tetraethylammonium (TEA) and N-methylnicotinamide (NMN), did not affect choline uptake in Caco-2 cells. Additionally, two typical p-glycoprotein substrates, daunomycin and verapamil, both inhibited choline accumulation. However the opposite was not true: choline did not inhibit DNM accumulation in Caco-2 cells. These results indicate the presence of a carrier-mediated transport system for choline in Caco-2 cells. The substrate specificity of this carrier is unlike that seen in the rat intestinal epithelium, and the human transport protein is distinct from those for TEA and NMN. P-glycoprotein substrates may inhibit choline uptake through specific or nonspecific interactions with the choline transporter.
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PMID:Choline uptake in human intestinal Caco-2 cells is carrier-mediated. 1288 45