Effect of Yi-nao-jie-yu decoction on γ-aminobutyric acid type A receptor in the hippocampus and serum inflammatory factors in a rat model of poststroke anxiety

Abstract Background: Gamma-aminobutyric acid type A (GABAA) receptors are thought to play a role in the functioning of the immune system. GABAA receptors have 19 types of subunits, the components of which determine their physiological functions. However, the subunits that are expressed in immune cells during inflammation have not been fully investigated. Recent reports have shown that anesthetic agents may affect the gene expression of GABAA receptors subunits in immune cells. Therefore, we aimed to investigate the changes in GABAA receptor subunit gene expression during macrophage differentiation and propofol administration in order to clarify the relationship between the expression of GABAA receptors and the immunomodulatory effect of propofol.Methods: Human acute monocytic leukemia (THP-1) cells were differentiated into macrophage-like cells (M0 THP-1); subsequently, M0 THP-1 cells were differentiated into inflammatory M1 macrophage-like cells (M1 THP-1). Propofol was administered during the differentiation into M1 THP-1 cells. Using reverse transcriptase polymerase chain reaction, we examined which GABAA receptor subunit genes were expressed and whether there were changes in the gene expression during macrophage differentiation and propofol administration in THP-1 cells.Results: The expression of the α1, α4, β1, β2, γ1, and γ2 subunits increased during differentiation into M0 THP-1 cells. The expression of the α1, α4, β1, β2, γ2, and δ subunits decreased and that of the γ1 subunit increased during differentiation into M1 THP-1 cells. The gene expression of the α1, α4, and β2 subunits increased upon administering propofol during differentiation into M1 THP-1 cells.Conclusions: The gene expression of GABAA receptor subunits changed during macrophage differentiation in THP-1 cells. The expressions of α1 and α4 increased following propofol administration during the differentiation into M1 THP-1 cells, which may indicate that the GABAA receptor is involved in the immunosuppressive effects of propofol. This study can help in the choice of anesthetic agents for proinflammatory conditions such as highly-invasive surgery.

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Classic Benzodiazepines Modulate the Open–Close Equilibrium in α1β2γ2Lγ-Aminobutyric Acid Type A Receptors

Anesthesiology ◽

10.1097/00000542-200504000-00014 ◽

2005 ◽

Vol 102 (4) ◽

pp. 783-792 ◽

Cited By ~ 45

Author(s):

Dirk Rüsch ◽

Stuart A. Forman

Keyword(s):

Gabaa Receptors ◽

Sulfonic Acid ◽

Site Occupancy ◽

Type A ◽

Aminobutyric Acid ◽

Clinical Effects ◽

Gamma Aminobutyric Acid ◽

Wild Type ◽

Acid Type ◽

Benzodiazepine Site

Background Classic benzodiazepine agonists induce their clinical effects by binding to a site on gamma-aminobutyric acid type A (GABAA) receptors and enhancing receptor activity. There are conflicting data regarding whether the benzodiazepine site is allosterically coupled to gamma-aminobutyric acid binding versus the channel open-close (gating) equilibrium. The authors tested the hypothesis that benzodiazepine site ligands modulate alpha1beta2gamma2L GABAA receptor gating both in the absence of orthosteric agonists and when the orthosteric sites are occupied. Methods GABAA receptors were recombinantly expressed in Xenopus oocytes and studied using two-microelectrode voltage clamp electrophysiology. To test gating effects in the absence of orthosteric agonist, the authors used spontaneously active GABAA receptors containing a leucine-to-threonine mutation at residue 264 on the alpha1 subunit. To examine effects on gating when orthosteric sites were fully occupied, they activated wild-type receptors with high concentrations of a partial agonist, piperidine-4-sulfonic acid. Results In the absence of orthosteric agonists, the channel activity of alpha1L264Tbeta2gamma2L receptors was increased by diazepam and midazolam and reduced by the inverse benzodiazepine agonist FG7142. Flumazenil displayed very weak agonism and blocked midazolam from further activating mutant channels. In wild-type receptors activated with saturating concentrations of piperidine-4-sulfonic acid, midazolam increased maximal efficacy. Conclusions Independent of orthosteric site occupancy, classic benzodiazepines modulate the gating equilibrium in alpha1beta2gamma2L GABAA receptors and are therefore allosteric coagonists. A Monod-Wyman-Changeux coagonist gating model quantitatively predicts these effects, suggesting that benzodiazepines minimally alter orthosteric ligand binding.

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Deficiency of glycosylated-α-dystroglycan in ventral hippocampus bridges the de-stabilization of gamma-aminobutyric acid type A receptors with the depressive-like behaviors of male mice

Biological Psychiatry ◽

10.1016/j.biopsych.2021.10.022 ◽

2021 ◽

Author(s):

Wen-Long Xie ◽

Hui-Ling Zheng ◽

Hou-Hong Li ◽

Jia-Jing Lu ◽

Shi-Ge Xue ◽

...

Keyword(s):

Type A ◽

Ventral Hippocampus ◽

Aminobutyric Acid ◽

Gamma Aminobutyric Acid ◽

Male Mice ◽

Acid Type

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Evidence of association between gamma-aminobutyric acid type A receptor genes located on 5q34 and female patients with mood disorders

Neuroscience Letters ◽

10.1016/s0304-3940(03)00611-6 ◽

2003 ◽

Vol 349 (1) ◽

pp. 9-12 ◽

Cited By ~ 32

Author(s):

K Yamada

Keyword(s):

Mood Disorders ◽

Type A ◽

Aminobutyric Acid ◽

Gamma Aminobutyric Acid ◽

Female Patients ◽

Acid Type

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