Ammonium carbonate의 GABAA 수용체 조절작용

Modulatory Effecet of Ammonium Carbonate on the GABAA Receptor

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 μM). 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 hyper-ammonemia.