Exogenous fructose 1,6-bisphosphate reduces K+ permeability in isolated rat hepatocytes.
The relationship between the protective effect of fructose 1,6-bisphosphate (F-1,6-P2) against cell injury and the modifications produced in the metabolic fluxes and in the membrane permeability to K+ was studied in isolated rat hepatocytes. Incubation of these cells in the presence of F-1,6-P2 reduced metabolic activity without affecting the ATP content, which suggests a downregulation of the ATP turnover. Using 86Rb+ as a tracer, we analyzed the relationship between these metabolic changes and alterations in K+ fluxes. In the presence of F-1,6-P2 the passive and the active K+ fluxes in hepatocytes decreased. However, the Na(+)-K+ pump from semipurified membranes was not directly affected by F-1,6-P2, which suggests a secondarily induced reduction of Na(+)-K+ pump activity. Moreover, galactosamine-treated cells showed a marked increase in permeability to K+ that was abolished by the presence of F-1,6-P2. This protective effect may be related to the prevention of K+ efflux. The results reported here strongly suggest the induction of channel arrest, and the associated metabolic downregulation, as the primary protective effect of F-1,6-P2, as has been shown in the prevention of galactosamine-induced hepatotoxicity.
Roig
T
T
Unitat de Biofísica, Facultat d'Odontologia, Universitat de Barcelona, Spain.
Bartrons
R
R
Bermúdez
J
J
D000818:Animals; D002118:Calcium; D002463:Cell Membrane Permeability / Q000187:drug effects; D002469:Cell Separation; D002614:Chelating Agents / Q000494:pharmacology; D004357:Drug Synergism; D004533:Egtazic Acid / Q000494:pharmacology; D005635:Fructosediphosphates / Q000494:pharmacology*; D005688:Galactosamine / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000378:metabolism*; D008297:Male; D011188:Potassium / Q000493:pharmacokinetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012413:Rubidium / Q000493:pharmacokinetics
D002614:Chelating Agents; D005635:Fructosediphosphates; D004533:Egtazic Acid; D005688:Galactosamine; C029063:fructose-1,6-diphosphate; D012413:Rubidium; D011188:Potassium; D002118:Calcium