AIM: To assess whether portacaval anastomosis (PCA)in rats affects the protein expression and/or activity of glutaminase in kidneys, intestines and in three brain areas of cortex, basal ganglia and cerebellum and to explain the neurological alterations found in hepatic encephalopathy (HE).METHODS: Sixteen male Wistar rats weighing 250-350g were grouped into sham-operation control (n=8) or portacaval shunt (n = 8). Twenty-eight days after the procedure, the animals were sacrificed. The duodenum,kidney and brain were removed, homogenised and mitochondria were isolated. Ammonia was measured in brain and blood. Phosphate-activated glutaminase (PAG)activity was determined by measuring ammonia production following incubation for one hour at 37℃ with O-phthalaldehyde (OPA) and specific activity expressed in units per gram of protein (μkat/g of protein). Protein expression was measured by immunoblotting.RESULTS: Duodenal and kidney PAG activities together with protein content were significantly higher in PCA group than in control or sham-operated rats (duodenum PAG activity was 976.95±268.87 μkat/g of protein in PCA rats vs 429.19±126.92. μkat/g of protein in shamoperated rats; kidneys PAG activity was 1259.18±228.79μkat/g protein in PCA rats vs 669.67±400.8 μkat/g of protein in controls, P＜0.05; duodenal protein content:173% in PCA vs sham-operated rats; in kidneys the content of protein was 152% in PCA vs sham-operated rats).PAG activity and protein expression in PCA rats were higher in cortex and basal ganglia than those in shamoperated rats (cortex: 6646.6 ± 1870.4 μkat/g of protein vs 3573.8±2037.4 μkat/g of protein in control rats,P＜0.01; basal ganglia, PAG activity was 3657.3±1469.6μkat/g of protein in PCA rats vs 2271.2 ± 384 μkat/g of protein in sham operated rats, P＜0.05; In the cerebellum, the PAG activity was 2471.6±701.4 μkat/g of protein vs 1452.9± 567.8 μkat/g of protein in the PCA and sham rats, respectively, P＜ 0.05; content of protein:cerebral cortex:162%±40% vs100% ± 26%, P＜ 0.009;and basal ganglia: 140%±39% vs 100%±14%,P＜0.05; but not in cerebellum: 100%±25% vs 100%±16%,P=ns).CONCLUSION: Increased PAG activity in kidney and duodenum could contribute significantly to the hyperammonaemia in PCA rats, animal model of encephalopathy.PAG is increased in non-synaptic mitochondria from the cortex and basal ganglia and could be implicated in the pathogenesis of hepatic encephalopathy. Therefore, PAG could be a possible target for the treatment of HE or liver dysfunction.