Luminal glucose enhances transepithelial Na⁺ and fluid transports in rat lungs

Abstract

The effects of luminal glucose on transepithelial Na⁺ and fluid transports were investigated in rat lungs. Two preparations were used: isolated, perfused lungs and lungs in situ perfused with blood (cross-circulations), a situation more comparable to that existing in vivo. Unidirectional (efflux from air spaces, J _out) and net (J _net) Na⁺ fluxes and fluid absorption from air spaces were estimated in lungs filled with bicarbonate-buffered solutions containing 10 mmol/l of either mannitol, glucose or α-methyl-D-glucopyranoside, or 0.1 mmol/l phlorizin in the presence of glucose. In the presence of mannitol J _out was estimated to be 7.8±1.02 pmol cm⁻² s⁻¹ in isolated lungs and 9.2±0.97 pmol cm⁻² s⁻¹ in lungs in situ, and J _net 1.0±0.33 and 2.5±0.35 pmol cm⁻² s⁻¹, respectively. When glucose replaced mannitol J _out (+30%+40%), J _net (+200%+300%) and fluid absorption (+100%+400%) were enhanced in both preparations. Substituting methyl glucoside for mannitol increased Na⁺ and fluid absorption rates to the same extent as glucose. Phlorizin, in the presence of glucose, reduced Na⁺ and fluid transports to values similar to those observed in the presence of mannitol. These changes did not result from modifications of the paracellular permeabilities (assessed with [³H]mannitol). It was concluded, in both isolated lungs and lungs in situ, that (a) the presence of glucose within air spaces accelerates both transepithelial Na⁺ and fluid transports, (b) increased Na⁺ transport is responsible for this larger fluid absorption, which exceeded threefold that the absorption of glucose alone would have produced, (c) most of this increase of transport rates is not the consequence of an increased glucose consumption providing a larger energy supply for ion transport, since the non-metabolizable analog methyl glucoside similarly enhanced transepithelial Na⁺ and fluid transports, and (d) the depressing effect of phlorizin on transepithelial Na⁺ transport indicates that the enhancement of Na⁺ transport by glucose is the consequence of increased Na⁺ entry across the apical membrane of respiratory epithelial cells through cotransport with glucose. It is proposed that glucose may play a role in the modulation of the epithelial lining fluid depth.