Acute ammonia treatment in vitro and in vivo inhibits the synthesis of a neuroprotectant kynurenic acid in rat cerebral cortical slices.
The synthesis of kynurenic acid (KYNA) from kynurenine was measured in the cerebral cortical slices. In vitro, ammonium acetate at the subtoxic to toxic concentration range from 1 mM to 10 mM dose-dependently inhibited KYNA synthesis (IC50=2.99 mM). Ammonia treatment in vivo decreased KYNA synthesis by 30%. These results suggest that impaired neuroprotection exerted by KYNA might be a potential contributor to the glutamate receptor-mediated aspect of acute ammonia neurotoxicity.
Saran
T
T
Department of Pharmacology and Toxicology, Medical University School, Jaczewskiego 8, 20-090 Lublin, Poland.
Hilgier
W
W
Kocki
T
T
Urbanska
E M
EM
Turski
W A
WA
Albrecht
J
J
D000085:Acetates / Q000494:pharmacology*; D000818:Animals; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D018691:Excitatory Amino Acid Antagonists / Q000378:metabolism*; D066298:In Vitro Techniques; D007736:Kynurenic Acid / Q000378:metabolism*; D008297:Male; D018696:Neuroprotective Agents / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar
D000085:Acetates; D018691:Excitatory Amino Acid Antagonists; D018696:Neuroprotective Agents; D007736:Kynurenic Acid; C018824:ammonium acetate