AJP - Cell Physiology, Vol 234, Issue 3 64-C72, Copyright © 1978 by American Physiological Society
Effects of phloretin and theophylline on 3-O-methylglucose transport by intestinal epithelial cells
J. Randles and G. A. Kimmich
Phloretin and theophylline each exert an immediate inhibitory effect on the
Na+-independent, facilitated-diffusion transport system for sugar
associated with intestinal epithelial cells. Phloretin inhibits
approximately 50% more of the total Na+-independent sugar flux than
theophylline. Neither agent has an immediate effect on the Na+-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 elevation of intracellular Na+. Other agents which elevate
cell Na+ also inhibit Na+-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+, the inhibitory effect on
Na+-dependent sugar flux tends to disappear. The slow-onset phloretin
effects are due to transinhibition of the Na+-dependent sugar carrier by
cellular Na+. 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+-dependent transport
systems.
