Modulatory Effect of Ammonium Carbonate on the GABAA Receptor.
- Author:
Jeoung Hee HA
1
;
Won Joon KIM
;
Han Ku MOON
Author Information
1. Department of Pharmacology, Yeungnam University, College of Medicine, Taegu, Korea.
- Publication Type:Original Article
- Keywords:
Ammonia;
GABAA receptor;
liver failure;
congenital hyperammonemia
- MeSH:
Ammonia;
Ammonium Compounds*;
Ataxia;
Carbon*;
gamma-Aminobutyric Acid;
Hyperammonemia;
Lethargy;
Liver Failure;
Muscimol;
Neurons;
Receptors, GABA;
Receptors, GABA-A;
Synaptic Transmission
- From:
Journal of the Korean Child Neurology Society
1998;6(1):39-46
- CountryRepublic of Korea
- Language:Korean
-
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.
