Modulatory effects of γ-hydroxybutyric acid on a GABAA receptor from crayfish muscle

Adelsberger, Helmuth; Brunswieck, Sönke; Dudél, J.

doi:10.1016/s0014-2999(98)00252-0

Cited by 4 publications

(3 citation statements)

References 17 publications

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“…Interestingly, the ␥2 chain of GABA A receptor was downregulated by the drug. This could be due to a sustained hyperstimulation because GABA A receptors seem to play a pivotal role in the functional and pharmacological effects of GHB (1,5,10,16,23,63). The majority of GABA A receptors contain a ␥2 subunit, expressed throughout the brain except in the thalamus.…”

Section: Discussionmentioning

confidence: 99%

“…The numbers of genes significantly affected and exhibiting some referenced Molecular Function terms were 252 (53.6%) in the hippocampus and 98 (57.0%) in the prefrontal cortex (Supplemental Table S1). 1 In the hippocampus, the Molecular Function GO terms modified by GHB treatment could be classified in three principal categories: 1) "binding" (GO: 0005488, P ϭ 4.23 ϫ 10 Ϫ5 , 40.73% of genes concerned), 2) "catalytic activity" (GO: 0003824, P ϭ 0.0029, 22.40% of genes concerned), and 3) "transcription regulator activity" (GO: 0030528, P ϭ 0.037, 6.31% of genes concerned) (Fig. 1).…”

Section: Molecular Functions Of Genes With Altered Expression After Tmentioning

confidence: 99%

“…The "binding" GO term was the most important in number of genes concerned and could be divided into nine significant 1 The online version of this article contains supplemental material. subgroups including "protein binding" (GO: 0005515, P ϭ 0.00231, 29.59% of genes concerned), "nucleic acid binding" (GO: 0003676, P ϭ 0.0168, 15.98% of genes concerned), and "transition metal ion binding" (GO: 0046914, P ϭ 0.0268, 11.83% of genes concerned).…”

Section: Molecular Functions Of Genes With Altered Expression After Tmentioning

confidence: 99%

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A single acute pharmacological dose of γ-hydroxybutyrate modifies multiple gene expression patterns in rat hippocampus and frontal cortex

Kemmel¹,

Klein²,

Dembélé

et al. 2010

Physiological Genomics

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Nyagan AG, Maitre M. A single acute pharmacological dose of ␥-hydroxybutyrate modifies multiple gene expression patterns in rat hippocampus and frontal cortex. Physiol Genomics 41: 146-160, 2010. First published January 26, 2010 doi:10.1152/physiolgenomics.00208.2009.-␥-Hydroxybutyrate (GHB) is a natural brain neuromodulator that has its own enzymatic machinery for synthesis and degradation, release, and transport systems and several receptors that belong to the G protein-coupled receptor (GPCR) family. Targeting of this system with exogenous GHB is used in therapy to induce sleep and anesthesia and to reduce alcohol withdrawal syndrome. GHB is also popular as a recreational drug for its anxiolytic and mild euphoric effects. However, in both cases, GHB must be administered at high doses in order to maintain GHB concentrations in brain of ϳ800 -1,000 M. These high concentrations are thought to be necessary for interactions with lowaffinity sites on GABA B receptor, but the molecular targets and cellular mechanisms modulated by GHB remain poorly characterized. Therefore, to provide new insights into the elucidation of GHB mechanisms of action and open new tracks for future investigations, we explored changes of GHB-induced transcriptomes in rat hippocampus and prefrontal cortex by using DNA microarray studies. We demonstrate that a single acute anesthetic dose of 1 g/kg GHB alters a large number of genes, 121 in hippocampus and 53 in prefrontal cortex; 16 genes were modified simultaneously in both brain regions. In terms of molecular functions, the majority of modified genes coded for proteins or nucleotide binding sites. In terms of Gene Ontology (GO) functional categories, the largest groups were involved in metabolic processing for hippocampal genes and in biological regulation for prefrontal cortex genes. The majority of genes modified in both structures were implicated in cell communication processes. Western blot and immunohistochemical studies carried out on eight selected proteins confirmed the microarray findings.potentiation of brain ␥-aminobutyric acid synapses; sleep and anesthesia; neuroprotection and cell signaling THE IDEA that ␥-hydroxybutyrate (GHB) possesses important functions as a neuromodulator in brain is now supported by numerous results (49). This endogenous compound is synthesized from GABA and is coreleased with it during GABA synaptic activity (51). Endogenous GHB concentrations in brain tissue range from 0.5-1 M to 10-25 M (22) but the fluctuations of GHB in the extracellular spaces, namely in the synapses, have never been measured. Successively, specific GHB binding was described in the brain of several animal species and in humans (6, 13, 31), and more recently GHB receptors have been cloned from both human and rat brain (2, 3). These GHB receptors appear to be heterogeneous with respect to their architecture and pharmacology, despite the fact they belong to G protein-coupled receptor (GPCR) classes. In particular, the GHB analog NCS-382 possesses antagonistic, partial agonist, or no...

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Section: Discussionmentioning

confidence: 99%

Section: Molecular Functions Of Genes With Altered Expression After Tmentioning

confidence: 99%

Section: Molecular Functions Of Genes With Altered Expression After Tmentioning

confidence: 99%

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A single acute pharmacological dose of γ-hydroxybutyrate modifies multiple gene expression patterns in rat hippocampus and frontal cortex

Kemmel¹,

Klein²,

Dembélé

et al. 2010

Physiological Genomics

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Crustacean Neuromuscular Glutamatergic and GABAergic Channels with Some Comparison to Drosophila Channels

Dudél¹,

Adelsberger²,

Heckmann³

2002

The Crustacean Nervous System

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Distribution and quantitative detection of GABAA receptor in Carassius auratus gibelio

Ruan

Zhang

et al. 2014

Fish Physiol Biochem

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Gamma-aminobutyric acid (GABA), a major inhibitory neurotransmitter in brain, is synthesized from glutamate and metabolized to succinic semialdehyde by glutamic acid decarboxylase (GAD) and GABA transaminase (GABA-T), respectively. The fast inhibitory effect of GABA is mediated by GABA type A (GABAA) receptors that are associated with several neurological disorders, and GABAA receptors are targets of several therapeutic agents. To date, information on the distribution and quantity of GABAA receptors in Carassius auratus gibelio is still limited. We investigated for the first time, the tissue-specific distribution of GABAARβ2a and GABAARβ2b, the two subunits of the predominant GABAA receptor subtype (α1β2γ2), and then, the expression of GABAARβ2a, GABAARβ2b, GAD, and quantified GABA-T genes in different tissues by quantitative real-time PCR method and compared different expressions between two developmental stages of C. auratus gibelio. Results showed that GABAARβ2a and GABAARβ2b genes expressed in both brain and peripheral organs using reverse transcription-polymerase chain reaction. In addition, the majority of GABAARβ2a, GABAARβ2b, GAD, and GABA-T were mainly synthesized in brain; however, a considerable amount of GABA-T was secreted from the peripheral tissues, especially in the liver. Moreover, the expression of GABAARβ2a and GABAARβ2b genes in different tissues varied with body weight change. This study provides a reference for further studies on GABA and GABAA receptors subunits and an insight on the possible pharmacological properties of the GABAA receptor in C. auratus gibelio.

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Modulatory effects of γ-hydroxybutyric acid on a GABAA receptor from crayfish muscle

Cited by 4 publications

References 17 publications

A single acute pharmacological dose of γ-hydroxybutyrate modifies multiple gene expression patterns in rat hippocampus and frontal cortex

A single acute pharmacological dose of γ-hydroxybutyrate modifies multiple gene expression patterns in rat hippocampus and frontal cortex

Crustacean Neuromuscular Glutamatergic and GABAergic Channels with Some Comparison to Drosophila Channels

Distribution and quantitative detection of GABAA receptor in Carassius auratus gibelio

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