Effect of portacaval anastomosis on electrically stimulated release of glutamate from rat hippocampal slices.

To evaluate the effects of chronic liver failure on release of the excitatory transmitter glutamate, electrically stimulated Ca2(+)-dependent and Ca2(+)-independent release of glutamate in the absence or presence of NH4+ was studied in superfused slices of hippocampus from portacaval-shunted or sham-operated rats 4 weeks after surgery. Spontaneous and stimulation-evoked release of glutamate was higher in shunted rats in the presence of normal or low Ca2+ concentrations, and this release was depressed by 5 mM ammonium chloride. These findings suggest that portacaval shunting results in increased levels of extracellular glutamate in brain, probably due to a decreased reuptake of glutamate into perineuronal astrocytes, shown in previous studies to undergo neuropathological changes following portacaval shunting. Changes in the inactivation of transmitter glutamate could be responsible, at least in part, for the neurological dysfunction resulting from sustained hyperammonemia and portal-systemic shunting resulting from chronic liver failure.