Effects of phloretin and theophylline on 3-O-methylglucose transport by intestinal epithelial cells
Phloretin and theophylline each exert an immediate inhibitory effect on the Na/sup +/-independent, facilitated-diffusion transport system for sugar associated with intestinal epithelial cells. Phloretin inhibits approximately 50% more of the total Na/sup +/-independent sugar flux than theophylline. Neither agent has an immediate effect on the Na/sup +/-dependent, concentrative sugar transport system, although preincubation of the cells with phloretin causes a significant inhibition. The slowly developing effect is correlated with a decrease in cellular adenosine triphosphate (ATP) and an evaluation of intracellular Na/sup +/. Other agents which elevate cell Na/sup +/ also inhibit Na/sup +/-dependent sugar influx, even if ATP levels are not depleted. On the other hand, if ATP is depleted by phloretin under conditions in which the cells do not gain Na/sup +/, the inhibitory effect on Na/sup +/-dependent sugar flux tends to disappear. The slow-onset phloretin effects are due to transinhibition of the Na/sup +/-dependent sugar carrier by cellular Na/sup +/. When the passive sugar carrier is inhibited by phloretin or theophylline, the concentrative system can establish an enhanced sugar gradient. Because of the secondary metabolic effects of phloretin, theophylline induces a greater gradient enhancement despite its more limited effect on the passive sugar-transport system. Sugar gradients as large as 20-fold are induced by theophylline, in contrast to 12-fold gradients observed in the presence of phloretin and approximately 7- to 8-fold for untreated cells. These results are discussed in terms of conceptual questions regarding the energetics of Na/sup +/-dependent transport systems.
- OSTI ID:
- 6467479
- Country of Publication:
- United States
- Language:
- English
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THEOPHYLLINE
BIOLOGICAL EFFECTS
ANIMAL CELLS
ATP
DRUGS
EPITHELIUM
INHIBITION
METABOLISM
SODIUM
ALKALI METALS
BODY
DIURETICS
ELEMENTS
HETEROCYCLIC COMPOUNDS
METALS
NUCLEOTIDES
ORGANIC COMPOUNDS
ORGANIC NITROGEN COMPOUNDS
ORGANIC OXYGEN COMPOUNDS
PURINES
TISSUES
XANTHINES
550300* - Cytology
551000 - Physiological Systems