Ammonia upregulates kynurenine aminotransferase II mRNA expression in rat brain: a role for astrocytic NMDA receptors?

Abstract	Kynurenine aminotransferase II (KAT-II) is the astrocytic enzyme catalyzing the synthesis of kynurenic acid (KYNA), an endogenous inhibitor of the α7-nicotinic receptor and the NMDA receptor (NMDAr). A previous study demonstrated an increase of KYNA synthesis in the brain of rats with thioacetamide (TAA)-induced acute liver failure. Here we show that TAA administration increases KAT-II expression in the rat cerebral cortex and the effect is mimicked in cerebral cortical astrocytes in culture treated with high (5 mM) concentration of ammonia. KAT-II expression in control and TAA-treated rats was increased by NMDAr antagonist memantine, and the effects of TAA and memantine appeared additive. In astrocytes, the NMDAr antagonist MK-801 raised KAT-II expression as well, while NMDA added alone had no effect. Glutamate decreased KAT-II mRNA level, which was attenuated by MK-801. The results suggest that stimulation of KAT-II expression during hepatic encephalopathy may be associated with a partial inactivation of astrocytic NMDAr by ammonia.
Authors	Marta Obara-Michlewska, Paulina Tuszyńska, Jan Albrecht
Journal	Metabolic brain disease (Metab Brain Dis) Vol. 28 Issue 2 Pg. 161-5 (Jun 2013) ISSN: 1573-7365 [Electronic] United States
PMID	23132651 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
Chemical References	Carcinogens Excitatory Amino Acid Antagonists RNA, Messenger Receptors, N-Methyl-D-Aspartate Thioacetamide Dizocilpine Maleate Ammonia Transaminases kynurenine-oxoglutarate transaminase Memantine
Topics	Ammonia (metabolism) Analysis of Variance Animals Astrocytes (drug effects, metabolism) Brain Chemistry (drug effects, physiology) Carcinogens (toxicity) Chemical and Drug Induced Liver Injury (metabolism, pathology) Dizocilpine Maleate (pharmacology) Excitatory Amino Acid Antagonists (pharmacology) Male Memantine (pharmacology) Primary Cell Culture RNA, Messenger (biosynthesis, genetics) Rats Rats, Sprague-Dawley Real-Time Polymerase Chain Reaction Receptors, N-Methyl-D-Aspartate (metabolism) Thioacetamide (toxicity) Transaminases (biosynthesis, genetics) Up-Regulation (drug effects, physiology)

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