Evidence for a phloretin-sensitive glycerol transport mechanism in the perfused rat liver

Glycerol, water, and urea transport were studied in the perfused rat liver. When hypertonic glycerol (100 mM) was infused into the perfused rat liver, rapid equilibration of glycerol between the extracellular and intracellular space occurred and only small effects of osmotic water fluxes on liver mass and extracellular ion concentrations were observed. However, when phloretin (0.2 mmol/l) was present, addition (or removal) of glycerol (100 mmol/l) induced within seconds a marked and transient decrease (or increase) of both liver mass and effluent Na+ and K+ concentrations, suggestive of transient osmotic water shifts out of and/or into the cells. These effects were observed with glycerol but not with infusion of 1,2-propanediol, 1,3-propanediol, or ethanediol (100 mmol/l). Calculation of permeability coefficients for hepatocytes in the perfused rat liver revealed that in the absence of a transmembrane glycerol concentration gradient the glycerol permeability was decreased from 0.146 +/- 0.005 (n = 14) to 0.055 +/- 0.016 mu m/s (n = 4) in the presence of phloretin (200 mu M). Water permeability was not affected by phloretin [0.146 +/- 0.005 under control conditions (n = 12) vs. 0.157 +/- 0.006 mu m/s (n = 4) in the presence of phloretin]. Urea permeability was 0.131 +/- 0.008 mu/s (n = 5) and decreased to 0.061 +/- 0.003 mu m/s in the presence of phloretin. Glycerol and water permeability were inhibited in the presence of hypertonic glucose (200 mM) by 47 and 27%, respectively, but urea permeability was not affected by glucose.