Ammonia at pathophysiologically relevant concentrations activates kynurenic acid synthesis in cultured astrocytes and neurons.
The synthesis of the NMDA receptor glycine site antagonist kynurenic acid (KYNA) from exogenously added kynurenine was measured in cultured cerebral cortical neurons, cortical astrocytes and an oligodendroglial cell line OLN-93, incubated for 2 h in the presence or absence of ammonium acetate ("ammonia") at 0.1-10 mM concentration. In neurons ammonia stimulated KYNA synthesis to approximately 160-170% of control at 0.1-1.0mM, did not produce any effect at 2.5 and 5 mM, and inhibited the synthesis to approximately 80% of control at 10mM concentration. In astrocytes, a stimulation to approximately 200% of control occurred in the whole ammonia concentration range. No effect of ammonia was noted in OLN-93 cells. Increased KYNA synthesis may represent a cytoprotective response of astrocytes and neurons against the NMDA receptor-mediated cytotoxic activity of ammonia.
Wejksza
Katarzyna
K
Department of Virology and Immunology, Institute of Microbiology and Biotechnology, Maria Curie-Skłodowska University, Akademicka 19, 20-033 Lublin, Poland.
Rzeski
Wojciech
W
Turski
Waldemar A
WA
Hilgier
Wojciech
W
Dybel
Anna
A
Albrecht
Jan
J
D000641:Ammonia / Q000494:pharmacology*; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D007736:Kynurenic Acid / Q000378:metabolism*; D009474:Neurons / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D000641:Ammonia; D007736:Kynurenic Acid