Hauptseite > Publikationsdatenbank > Inhibition of glutamate/glutamine cycle in vivo results in decreased benzodiazepine binding and differentially regulated GABAergic subunit expression in the rat brain > print

001     10474
005     20210129210523.0
024 7 _ |2 pmid
|a pmid:20384720
024 7 _ |2 DOI
|a 10.1111/j.1528-1167.2010.02562.x
024 7 _ |2 WOS
|a WOS:000280669600013
037 _ _ |a PreJuSER-10474
041 _ _ |a eng
082 _ _ |a 610
084 _ _ |2 WoS
|a Clinical Neurology
100 1 _ |a Cremer, C.M.
|b 0
|u FZJ
|0 P:(DE-Juel1)VDB71164
245 _ _ |a Inhibition of glutamate/glutamine cycle in vivo results in decreased benzodiazepine binding and differentially regulated GABAergic subunit expression in the rat brain
260 _ _ |a Oxford [u.a.]
|b Wiley-Blackwell
|c 2010
300 _ _ |a 1446 - 1455
336 7 _ |a Journal Article
|0 PUB:(DE-HGF)16
|2 PUB:(DE-HGF)
336 7 _ |a Output Types/Journal article
|2 DataCite
336 7 _ |a Journal Article
|0 0
|2 EndNote
336 7 _ |a ARTICLE
|2 BibTeX
336 7 _ |a JOURNAL_ARTICLE
|2 ORCID
336 7 _ |a article
|2 DRIVER
440 _ 0 |a Epilepsia
|x 0013-9580
|0 12861
|y 8
|v 51
500 _ _ |a This study was partially supported by a grant of the Helmholtz Alliance in "Mental Health in an Ageing Society." We thank S. Buller, L. Igdalova, and S. Wilms for their excellent technical assistance.
520 _ _ |a 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.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 (GABA(A) , GABA(B) and GABA(A) -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 GABA(A) α₁ and γ₂ subunits (which primarily mediate BZ binding) by western blot analysis.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 (B(max)) on cerebral membrane homogenates 72 h after MSO treatment, without changes in binding site affinity (K(D)). Furthermore, we found differential changes of α₁ , γ₂ , and phosphorylated γ₂ subunits following MSO treatment.On the basis of our findings, we conclude that the glutamate/glutamine cycle directly influences GABAergic neurotransmission by regulating GABA(A) subunit composition, thereby affecting its modulation by endogenous benzodiazepines.
536 _ _ |0 G:(DE-Juel1)FUEK409
|2 G:(DE-HGF)
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|c FUEK409
|a Funktion und Dysfunktion des Nervensystems (FUEK409)
536 _ _ |a 89571 - Connectivity and Activity (POF2-89571)
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588 _ _ |a Dataset connected to Web of Science, Pubmed
650 _ 2 |2 MeSH
|a Animals
650 _ 2 |2 MeSH
|a Autoradiography: methods
650 _ 2 |2 MeSH
|a Benzodiazepines: metabolism
650 _ 2 |2 MeSH
|a Binding Sites: drug effects
650 _ 2 |2 MeSH
|a Brain: anatomy & histology
650 _ 2 |2 MeSH
|a Brain: drug effects
650 _ 2 |2 MeSH
|a Brain: metabolism
650 _ 2 |2 MeSH
|a Drug Interactions
650 _ 2 |2 MeSH
|a Enzyme Inhibitors: pharmacology
650 _ 2 |2 MeSH
|a Excitatory Amino Acid Antagonists: pharmacology
650 _ 2 |2 MeSH
|a Glutamate-Ammonia Ligase: metabolism
650 _ 2 |2 MeSH
|a Glutamic Acid: metabolism
650 _ 2 |2 MeSH
|a Glutamine: metabolism
650 _ 2 |2 MeSH
|a Male
650 _ 2 |2 MeSH
|a Methionine Sulfoximine: pharmacology
650 _ 2 |2 MeSH
|a Protein Binding: drug effects
650 _ 2 |2 MeSH
|a Protein Subunits: genetics
650 _ 2 |2 MeSH
|a Protein Subunits: metabolism
650 _ 2 |2 MeSH
|a RNA, Messenger: metabolism
650 _ 2 |2 MeSH
|a Rats
650 _ 2 |2 MeSH
|a Rats, Wistar
650 _ 2 |2 MeSH
|a Receptors, GABA: genetics
650 _ 2 |2 MeSH
|a Receptors, GABA: metabolism
650 _ 2 |2 MeSH
|a Time Factors
650 _ 2 |2 MeSH
|a Tritium: metabolism
650 _ 7 |0 0
|2 NLM Chemicals
|a Enzyme Inhibitors
650 _ 7 |0 0
|2 NLM Chemicals
|a Excitatory Amino Acid Antagonists
650 _ 7 |0 0
|2 NLM Chemicals
|a Protein Subunits
650 _ 7 |0 0
|2 NLM Chemicals
|a RNA, Messenger
650 _ 7 |0 0
|2 NLM Chemicals
|a Receptors, GABA
650 _ 7 |0 10028-17-8
|2 NLM Chemicals
|a Tritium
650 _ 7 |0 12794-10-4
|2 NLM Chemicals
|a Benzodiazepines
650 _ 7 |0 1982-67-8
|2 NLM Chemicals
|a Methionine Sulfoximine
650 _ 7 |0 56-85-9
|2 NLM Chemicals
|a Glutamine
650 _ 7 |0 56-86-0
|2 NLM Chemicals
|a Glutamic Acid
650 _ 7 |0 EC 6.3.1.2
|2 NLM Chemicals
|a Glutamate-Ammonia Ligase
650 _ 7 |a J
|2 WoSType
653 2 0 |2 Author
|a l-Methionine sulfoximine
653 2 0 |2 Author
|a Neurotransmitter receptors
653 2 0 |2 Author
|a GABA(A)
653 2 0 |2 Author
|a Benzodiazepine binding
653 2 0 |2 Author
|a Autoradiography
653 2 0 |2 Author
|a In situ hybridization
700 1 _ |a Bidmon, H.-J.
|b 1
|0 P:(DE-HGF)0
700 1 _ |a Görg, B.
|b 2
|0 P:(DE-HGF)0
700 1 _ |a Palomero-Gallagher, N.
|b 3
|u FZJ
|0 P:(DE-Juel1)VDB1208
700 1 _ |a Lopez Escobar, J.
|b 4
|u FZJ
|0 P:(DE-Juel1)VDB89117
700 1 _ |a Speckmann, E.-J.
|b 5
|0 P:(DE-HGF)0
700 1 _ |a Zilles, K.
|b 6
|u FZJ
|0 P:(DE-Juel1)131714
773 _ _ |a 10.1111/j.1528-1167.2010.02562.x
|g Vol. 51, p. 1446 - 1455
|p 1446 - 1455
|q 51<1446 - 1455
|0 PERI:(DE-600)2002194-X
|t Epilepsia
|v 51
|y 2010
|x 0013-9580
856 7 _ |u http://dx.doi.org/10.1111/j.1528-1167.2010.02562.x
909 C O |o oai:juser.fz-juelich.de:10474
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914 1 _ |y 2010
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