Effect of glutamine synthetase inhibition on brain and interorgan ammonia metabolism in bile duct ligated rats

Journal of Cerebral Blood Flow and Metabolism : Official Journal of the International Society of Cerebral Blood Flow and Metabolism
Andreas W FriesMichael Sørensen

Abstract

Ammonia has a key role in the development of hepatic encephalopathy (HE). In the brain, glutamine synthetase (GS) rapidly converts blood-borne ammonia into glutamine which in high concentrations may cause mitochondrial dysfunction and osmolytic brain edema. In astrocyte-neuron cocultures and brains of healthy rats, inhibition of GS by methionine sulfoximine (MSO) reduced glutamine synthesis and increased alanine synthesis. Here, we investigate effects of MSO on brain and interorgan ammonia metabolism in sham and bile duct ligated (BDL) rats. Concentrations of glutamine, glutamate, alanine, and aspartate and incorporation of (15)NH(4)(+) into these amino acids in brain, liver, muscle, kidney, and plasma were similar in sham and BDL rats treated with saline. Methionine sulfoximine reduced glutamine concentrations in liver, kidney, and plasma but not in brain and muscle; MSO reduced incorporation of (15)NH(4)(+) into glutamine in all tissues. It did not affect alanine concentrations in any of the tissues but plasma alanine concentration increased; incorporation of (15)NH(4)(+) into alanine was increased in brain in sham and BDL rats and in kidney in sham rats. It inhibited GS in all tissues examined but only in brain was an increa...Continue Reading

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Citations

Apr 29, 2014·Trends in Biochemical Sciences·Rui Wang
Sep 6, 2014·Cellular and Molecular Neurobiology·Xiang-en MengChen Yang
Feb 26, 2019·Journal of Neuroscience Research·Arne SchousboeUrsula Sonnewald
Dec 18, 2014·Metabolic Brain Disease·Yun Yan SuLong Jiang Zhang
Feb 6, 2017·Indian Journal of Clinical Biochemistry : IJCB·Sivamani KanimozhiSubramanian Sathishkumar

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