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

Abstract

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 microm/s (n = 4) in the presence of phloretin (200 microM). Water permeability was not affected by phloretin [0.146 +/- 0.005 under control conditions (n = 12) vs. 0.157 +/- 0.006 microm/s (n = 4) in the presence of phloretin]. Urea permeability was 0.131 +/- 0.008 microm/s (n = 5) and decreased to 0.061 +/- 0.003 microm/s in the presence ofphloretin. 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.

Biophysical assessment of aquaporin‐9 as principal facilitative pathway in mouse liver import of glucogenetic glycerol

“…This is also supported by the fact that the extent of phloretin inhibition is maximal at 18‐h starvation when the liver is found to feature its highest P gly (Figure 3D). Phloretin‐sensitive glycerol transport was also suggested in a previous study with perfused rat livers (vom Dahl and Haussinger 1997).…”

Vascular endoscopic and macroscopic observations after crush stenting of coronary artery bifurcations in pigs

“…The concentration of Ph required to cause a 50% decrease in hepatocyte cell viability (LD 50 ) in 2 h was >500 ± 50 µM [38]. These results are consistent with several other studies demonstrating that the cell viability of normal rat hepatocytes from in vivo perfused rat liver was unaffected by the infusion of Ph at 200 µmol/L [39, 40]. The results of this literature suggest that it may be possible to use the apple polyphenolic compound Ph for chemoprevention to reduce the growth of liver cancer cells and induce their apoptosis [41].…”

Urea Transporter Physiology Studied in Knockout Mice

“…Development of a UT inhibitor may have clinical significance in treating water overloaded diseases. Phloretin is a commonly used UT-B inhibitor experimentally, but its broad inhibitory activity, including inhibition transport of glucose (Lefevre and Marshall, 1959) and glycerol (vom Dahl and Haussinger, 1997), impedes its usage as a UT-B inhibitor. Urea analogs, such as methylurea, thiourea, and dimethylurea, competitively inhibit UT-B urea transport, usually at high concentrations (Zhao et al, 2007).…”