Common characteristics for Na+-dependent sugar transport in Caco-2 cells and human fetal colon.
The recent demonstration that the human colon adenocarcinoma cell line Caco-2 was susceptible to spontaneous enterocytic differentiation led us to consider the question as to whether Caco-2 cells would exhibit sodium-coupled transport of sugars. This problem was investigated using isotopic tracer flux measurements of the nonmetabolizable sugar analog alpha-methylglucoside (AMG). AMG accumulation in confluent monolayers was inhibited to the same extent by sodium replacement, 200 microM phlorizin, 1 mM phloretin, and 25 mM D-glucose, but was not inhibited further in the presence of both phlorizin and phloretin. Kinetic studies were compatible with the presence of both a simple diffusive process and a single, Na+-dependent, phlorizin- and phloretin-sensitive AMG transport system. These results also ruled out any interaction between AMG and a Na+-independent, phloretin-sensitive, facilitated diffusion pathway. The brush-border membrane localization of the Na+-dependent system was inferred from the observations that its functional differentiation was synchronous with the development of brush-border membrane enzyme activities and that phlorizin and phloretin addition 1 hr after initiating sugar transport produced immediate inhibition of AMG uptake as compared to ouabain. Finally, it was shown that brush-border membrane vesicles isolated from the human fetal colonic mucosa do possess a Na+-dependent transport pathway(s) for D-glucose which was inhibited by AMG and both phlorizin and phloretin. Caco-2 cells thus appear as a valuable cell culture model to study the mechanisms involved in the differentiation and regulation of intestinal transport functions.
D000230:Adenocarcinoma; D001693:Biological Transport, Active / Q000187:drug effects; D002460:Cell Line; D002478:Cells, Cultured; D003106:Colon / Q000378:metabolism*; D003110:Colonic Neoplasms; D005333:Fetus; D006801:Humans; D006867:Hydrolases / Q000378:metabolism; D007700:Kinetics; D008353:Mannitol / Q000378:metabolism; D008757:Methylglucosides / Q000378:metabolism; D008871:Microvilli / Q000201:enzymology; D009005:Monosaccharides / Q000378:metabolism*; D012964:Sodium / Q000494:pharmacology*
D008757:Methylglucosides; D009005:Monosaccharides; D008353:Mannitol; C027020:methylglucoside; D012964:Sodium; D006867:Hydrolases