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Journal of the Korean Child Neurology Society 1998;6(1):39-46.
Published online October 30, 1998.
Modulatory Effect of Ammonium Carbonate on the GABAA Receptor.
Jeoung Hee Ha, Won Joon Kim, Han Ku Moon
1Department of Pharmacology, Yeungnam University, College of Medicine, Taegu, Korea.
2Department of Pediatrics, Yeungnam University, College of Medicine, Taegu, Korea.
Abstract
PURPOSE
This study was aimed to investigate the modulatory effect of ammonium carbonate on the GABAA receptor. METHODS: The effects of ammonium carbonate on the binding of radioligands to components of the GABAA receptor complex were observed. RESULTS: [3H]Flunitrazepam binding to the benzodiazepine receptor was enhanced by ammonium (<800 micrometer). Further increasing ammonium carbonate concentrations decreased [3H]flunitrazepam binding to control levels. Furthermore, GABA and muscimol increased the potency of ammonium carbonate in enhancing [3H]flunitrazepam binding. Ammonium carbonate also increased, then decreased the binding of 10nM [3H]muscimol binding to the GABAA receptor in a concentration-dependent manner. More importantly, the presence of ammonia along with a benzodiazepine receptor agonist synergistically enhanced [3H]muscimol binding to the GABA receptor. CONCLUSION: These suggest that ammonia may enhance GABAergic neurotransmission at concentrations commonly encountered in hepatic failure, then suppress the inhibitory neuronal function observed at higher (>1mM) ammonia concentrations. This increase in GABAergic neurotransmission is consistent with the clinical picture of lethargy, ataxia and cognitive deficits associated with liver failure and congenital hyperammonemia.
Key Words: Ammonia, GABAA receptor, liver failure, congenital hyperammonemia
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