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• W1530046457 abstract "Purpose: The astrocytic enzyme glutamine synthetase (GS) is a key regulator of glutamate and γ-aminobutyric acid (GABA) metabolism in the glutamate/glutamine cycle (GGC). Inhibition of GS results in changes of neurotransmitter release and recycling. However, little is known about the influence of GGC on neurotransmitter receptor expression. In the pentylenetetrazole model of epilepsy, GS becomes nitrated and partially inhibited, and we demonstrated alterations of neurotransmitter receptor expression in the same model. Therefore, we hypothesized similar changes of neurotransmitter receptor expression when GS is inhibited in vivo. Methods: Rats were treated with a single dose (100 mg/kg bodyweight) of l-methionine sulfoximine (MSO), an irreversible inhibitor of GS. We used 3H-receptor autoradiography to measure glutamatergic [α-amino-3-hydroxy-5-methyl-4-isoxazol-propionic acid (AMPA), kainate, N-methyl-d-aspartate (NMDA)], GABAergic (GABAA, GABAB and GABAA-associated benzodiazepine (BZ) binding sites], dopamine D1, and adenosine A1 receptor subtypes. In addition, we performed saturation analysis of BZ binding sites on cerebral membrane homogenates and investigated the expression of GABAAα1 and γ2 subunits (which primarily mediate BZ binding) by western blot analysis. Results: We demonstrated a significant reduction of BZ binding in the somatosensory, piriform, and entorhinal cortices and in the amygdala, 24 and 72 h after MSO treatment. Saturation analysis revealed decreased BZ binding (Bmax) on cerebral membrane homogenates 72 h after MSO treatment, without changes in binding site affinity (KD). Furthermore, we found differential changes of α1, γ2, and phosphorylated γ2 subunits following MSO treatment. Conclusion: On the basis of our findings, we conclude that the glutamate/glutamine cycle directly influences GABAergic neurotransmission by regulating GABAA subunit composition, thereby affecting its modulation by endogenous benzodiazepines." @default.
• W1530046457 created "2016-06-24" @default.
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• W1530046457 date "2010-04-02" @default.
• W1530046457 modified "2023-10-16" @default.
• W1530046457 title "Inhibition of glutamate/glutamine cycle in vivo results in decreased benzodiazepine binding and differentially regulated GABAergic subunit expression in the rat brain" @default.
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• W1530046457 doi "https://doi.org/10.1111/j.1528-1167.2010.02562.x" @default.
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