Sensitization of stress-induced feeding in rats repeatedly exposed to brief restraint: the role of corticosterone |
| |
Authors: | Jeoung-Hee Ha and Anthony S. Basile |
| |
Affiliation: | Laboratory of Neuroscience, Building 8, Room 111. NIDDKD, National Institutes of Health, Bethesda, MD 20892, USA |
| |
Abstract: | The effects of 5-500 μM concentrations of neutral ammonium salts on the binding of ligands to components of the GABAA receptor complex were investigated. [3H]Flunitrazepam binding to the benzodiazepine receptor was enhanced by ammonium (10–500 μM), but not sodium tartrate with EC50 = 98 μM and Emax = 31%. Further increasing ammonium tartrate concentrations (500–2500 μM) decreased [3H]flunitrazepam binding to control levels. The ammonium tartrate-induced increase in [3H]flunitrazepam binding was manifested as a 50% decrease in Kd. Furthermore, GABA increased the potency of ammonium tartrate in enhancing [3H]flunitrazepam binding by 63%. [3H]Ro 15-1788 and [3H]Ro 15-4513 binding to the benzodiazepine receptor was not significantly enhanced by ammonium tartrate (Emax ≈ 13%). Ammonium tartrate also increased, then decreased the binding of 500 nM [3H]muscimol to the GABAA receptor (EC50 = 52 μM, Emax = 30%) in a concentration-dependent manner, but had no effect on [3H]SR 95-531 binding (Emax < 16%). The ammonium tartrate-induced alterations in [3H]muscimol binding were demonstrated in saturation assays as the loss of the high affinity binding site and a 27% increase in the Bmax of the low affinity binding site. These results indicate that ammonia biphasically enhances, then returns ligand binding to both the GABA and benzodiazepine receptor components of the GABAA receptor complex to control levels in a barbiturate-like fashion. This suggests that ammonia may enhance GABAergic neurotransmission at concentrations commonly encountered in hepatic failure, an event preceding the suppression of inhibitory neuronal function observed at higher ( > 1 mM) 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. |
| |
Keywords: | Ammonia Muscimol Flunitrazepam GABAA receptor Liver failure |
本文献已被 ScienceDirect 等数据库收录! |
|