EXOGENOUS FRUCTOSE-1,6-BISPHOSPHATE REDUCES K+ PERMEABILITY IN ISOLATED RAT HEPATOCYTES

The relationship between the protective effect of fructose 1,6-bisphos phate (F-1,6-P-2) against cell injury and the modifications produced i n the metabolic fluxes and in the membrane permeability to K+ was stud ied in isolated rat hepatocytes. Incubation of these cells in the pres ence of F-1,6-P-2 reduced metabolic activity without affecting the ATP content, which suggests a downregulation of the ATP turnover. Using R b-86(+) as a tracer, we analyzed the relationship between these metabo lic changes and alterations in K+ fluxes. In the presence of F-1,6-P-2 the passive and the active K+ fluxes in hepatocytes decreased. Howeve r, the Na+-K+ pump from semipurified membranes was not directly affect ed by F-1,6-P-2, which suggests a secondarily induced reduction of Na-K+ pump activity. Moreover, galactosamine-treated cells showed a mark ed increase in permeability to K+ that was abolished by the presence o f F-1,6-P-2. This protective effect may be related to the prevention o f 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-P-2, as has been shown in the prev ention of galactosamine-induced hepatotoxicity.