Inhibition of the serosal sugar carrier in isolated intestinal epithelial cells by saccharin.
Isolated intestinal cells accumulate certain monosaccharides via an Na+-dependent, active transport system localized in the brush-border membrane, and release sugar molecules at the basolateral boundary via a facilitated diffusion, passive system. Work described here indicates that sodium saccharin (25-130 mM) has little if any direct effect on the active transport system, but that the passive transport system is inhibited by saccharin. A short period of exposure (10-60 min) is required for expression of the effect, which is detectable at saccharin concentrations as low as 10 mM. At 100 mM-sodium saccharin, as much as 50% inhibition occurs. Saccharin also appears to act as a weak metabolic inhibitor. The basis of the 'non-specific' effect is not understood, but it can compromise the capacity of the epithelial cells to form sugar gradients. When a sugar is accumulated that satisfies both transport systems (for example 3-O-methylglucose) the effect of saccharin on the passive transport system is the predominant one, and the cells establish a higher sugar gradient than that observed in the absence of saccharin. The 'non-specific' metabolic effect is manifested as an inhibition of sugar gradient formation when sugars that satisfy only the active system (such as alpha-methylglucoside) are accumulated.
Kimmich
G A
GA
Department of Biochemistry, University of Rochester, NY 14642.
Randles
J
J
Anderson
R L
RL
D000818:Animals; D002645:Chickens; D003847:Deoxyglucose / Q000378:metabolism; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D066298:In Vitro Techniques; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000187:drug effects*; D008757:Methylglucosides / Q000378:metabolism; D009004:Monosaccharide Transport Proteins / Q000037:antagonists & inhibitors*; D012439:Saccharin / Q000633:toxicity*; D012964:Sodium / Q000378:metabolism
D008757:Methylglucosides; D009004:Monosaccharide Transport Proteins; C027020:methylglucoside; D003847:Deoxyglucose; D012964:Sodium; D012439:Saccharin