J Korean Child Neurol Soc.
1998 Oct;6(1):39-46.
Modulatory Effect of Ammonium Carbonate on the GABAA Receptor
- Affiliations
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- 1Department of Pharmacology, Yeungnam University, College of Medicine, Taegu, Korea.
- 2Department of Pediatrics, Yeungnam University, College of Medicine, Taegu, Korea.
Abstract
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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.