title: 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.affiliation: Department of Neurotoxicology, Mossakowski Medical Research Centre, Polish Academy of Sciences, Warsaw, Poland. martomich@gmail.com
authors.forename: Marta
authors.initials: M
authors.lastname: Obara-Michlewska
authors.forename: Paulina
authors.initials: P
authors.lastname: Tuszyńska
authors.forename: Jan
authors.initials: J
authors.lastname: Albrecht
mesh_terms: D000641:Ammonia / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000378:metabolism*; D001923:Brain Chemistry / Q000187:drug effects / Q000502:physiology*; D002273:Carcinogens / Q000633:toxicity; D056486:Chemical and Drug Induced Liver Injury / Q000378:metabolism / Q000473:pathology; D016291:Dizocilpine Maleate / Q000494:pharmacology; D018691:Excitatory Amino Acid Antagonists / Q000494:pharmacology; D008297:Male; D008559:Memantine / Q000494:pharmacology; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000096:biosynthesis* / Q000235:genetics*; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction; D016194:Receptors, N-Methyl-D-Aspartate / Q000378:metabolism*; D013853:Thioacetamide / Q000633:toxicity; D000637:Transaminases / Q000096:biosynthesis* / Q000235:genetics*; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
chemical_list: D002273:Carcinogens; D018691:Excitatory Amino Acid Antagonists; D012333:RNA, Messenger; D016194:Receptors, N-Methyl-D-Aspartate; D013853:Thioacetamide; D016291:Dizocilpine Maleate; D000641:Ammonia; D000637:Transaminases; C021481:kynurenine-oxoglutarate transaminase; D008559:Memantine