Phlorizin increases the permeability of intestinal mucosal membrane to sodium

We reported previously that when jejunal transmural glucose transport was inhibited by phlorizin the ratio of Na:giucose transport increased from 2.0:1 (in controls) to 3.3:1. To elucidate the mechanism of this increased ratio of Na:glucose transport, in the present study we have investigated the effect of phlorizin on Na uptake by brush border membrane vesicles and by everted sacs of hamster jejunum. In experiments on membrane vesicles the following observations were made. The time course of Na uptake showed that the control vesicles were in complete equilibrium with a Na-containing (100 mM) medium between 30 and 90 min incubation. In these periods of incubation, the vesicles incubated with phlorizin presumably also equilibrated with the medium, but lost their intravesicular Na during Millipore filtration and washing, and consequently the residual Na content was lower than that of controls. This effect of phlorizin was concentration dependent, and appeared to be unrelated to Na-coupled glucose transport, because it was also observed in the absence of glucose. This loss of Na during Millipore filtration and washing was also observed (i) when vesicles were equilibrated in a Na-containing solution in the absence of phlorizin and then exposed to a similar solution containing phlorizin, or (ii) when vesicles were equilibrated in a Na-containing solution in the presence of phlorizin and then washed repeatedly following Millipore filtration. Preincubation of vesicles for 10 min in a Na- and glucose-free solution containing phlorizin followed by incubation for 30–90 s in solutions containing 1 mM glucose and various concentrations of Na (from 10 to 100 mM) caused an increase in Na uptake from all concentrations of Na. After similar preincubation, when jejunal everted sacs were incubated for 15 s in a Na- and glucose-containing medium, Na uptake by the sacs increased. These findings suggest that phlorizin causes an increase in permeability of mucosal membrane of the enterocyte to Na. This may cause a rapid dissipation of Na gradient and an increase in the ratio of Na:glucose transport. The dissipation of Na gradient may be an additional mechanism for phlorizin-induced inhibition of intestinal sugar transport.