201. Ammonia upregulates kynurenine aminotransferase II mRNA expression in rat brain: a role for astrocytic NMDA receptors?
- Author
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Jan Albrecht, Paulina Tuszyńska, and Marta Obara-Michlewska
- Subjects
Male ,medicine.medical_specialty ,Primary Cell Culture ,Stimulation ,Thioacetamide ,Real-Time Polymerase Chain Reaction ,Receptors, N-Methyl-D-Aspartate ,Biochemistry ,Rats, Sprague-Dawley ,Cellular and Molecular Neuroscience ,chemistry.chemical_compound ,Kynurenic acid ,Ammonia ,Memantine ,Internal medicine ,medicine ,Animals ,RNA, Messenger ,Receptor ,Transaminases ,Brain Chemistry ,Analysis of Variance ,biology ,Chemistry ,Glutamate receptor ,Antagonist ,Kynurenine aminotransferase II ,Rats ,Up-Regulation ,Endocrinology ,Astrocytes ,Carcinogens ,NMDA receptor ,Neurology (clinical) ,Chemical and Drug Induced Liver Injury ,Dizocilpine Maleate ,biology.gene ,Excitatory Amino Acid Antagonists ,medicine.drug - 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.
- Published
- 2012