scholarly journals Neural Mechanisms of Sevoflurane-induced Respiratory Depression in Newborn Rats

2008 ◽  
Vol 109 (2) ◽  
pp. 233-242 ◽  
Author(s):  
Junya Kuribayashi ◽  
Shigeki Sakuraba ◽  
Masanori Kashiwagi ◽  
Eiki Hatori ◽  
Miki Tsujita ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Respiratory Depression ◽  
Motor Neurons ◽  
Type A ◽  
Aminobutyric Acid ◽  
Respiratory Neurons ◽  
Gamma Aminobutyric Acid ◽  
Inspiratory Neurons ◽  
Acid Type ◽  
Bötzinger Complex

Background Sevoflurane-induced respiratory depression has been reported to be due to the action on medullary respiratory and phrenic motor neurons. These results were obtained from extracellular recordings of the neurons. Here, the authors made intracellular recordings of respiratory neurons and analyzed their membrane properties during sevoflurane application. Furthermore, they clarified the role of gamma-aminobutyric acid type A receptors in sevoflurane-induced respiratory depression. Methods In the isolated brainstem-spinal cord of newborn rat, the authors recorded the C4 nerve burst as an index of inspiratory activity. The preparation was superfused with a solution containing sevoflurane alone or sevoflurane plus the gamma-aminobutyric acid type A receptor antagonist picrotoxin or bicuculline. Neuronal activities were also recorded using patch clamp techniques. Results Sevoflurane decreased C4 burst rate and amplitude. Separate perfusion of sevoflurane to the medulla and to the spinal cord decreased C4 burst rate and amplitude, respectively. Both picrotoxin and bicuculline attenuated the reduction of C4 burst rate. Sevoflurane reduced both intraburst firing frequency and membrane resistance of respiratory neurons except for inspiratory neurons. Conclusion Under the influence of sevoflurane, the region containing inspiratory neurons, i.e., the pre-Bötzinger complex, may determine the inspiratory rhythm, because reduced C4 bursts were still synchronized with the bursts of inspiratory neurons within the pre-Bötzinger complex. In contrast, the sevoflurane-induced decrease in C4 burst amplitude is mediated through the inhibition of phrenic motor neurons. gamma-Aminobutyric acid type A receptors may be involved in the sevoflurane-induced respiratory depression within the medulla, but not within the spinal cord.

[11C]Flumazenil Positron Emission Tomography Analyses of Brain Gamma-Aminobutyric Acid Type A Receptors in Angelman Syndrome

2008 ◽  
Vol 152 (4) ◽  
pp. 546-549.e3 ◽  
Author(s):  
Naoko Asahina ◽  
Tohru Shiga ◽  
Kiyoshi Egawa ◽  
Hideaki Shiraishi ◽  
Shinobu Kohsaka ◽  
...  
Keyword(s):  
Positron Emission Tomography ◽  
Angelman Syndrome ◽  
Type A ◽  
Emission Tomography ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Positron Emission ◽  
Acid Type

Autoradiographic Localization of the Gamma-Aminobutyric Acid Type A Receptor Agonist 3H-Muscimol in the Rat Superior Cervical Ganglion

Pharmacology ◽  
1992 ◽  
Vol 44 (2) ◽  
pp. 107-112 ◽  
Author(s):  
Francesco Amenta ◽  
Elena Bronzetti ◽  
Carlo Cavallotti ◽  
Laura Felici ◽  
Fabio Ferrante ◽  
...  
Keyword(s):  
Superior Cervical Ganglion ◽  
Receptor Agonist ◽  
Type A ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Acid Type ◽  
Cervical Ganglion

scholarly journals Modifications in Gamma-aminobutyric Acid type A Receptor Subunit Gene Expression During Macrophage Differentiation and Propofol Administration in THP-1 Cells

2021 ◽  
Author(s):  
Tsukasa Kochiyama ◽  
Izumi Kawagoe ◽  
Ai Yamaguchi ◽  
Masataka Fukuda ◽  
Masakazu Hayashida
Keyword(s):  
Gene Expression ◽  
Immune Cells ◽  
Type A ◽  
Aminobutyric Acid ◽  
Receptor Subunit ◽  
Gamma Aminobutyric Acid ◽  
Subunit Gene ◽  
Macrophage Differentiation ◽  
Anesthetic Agents ◽  
Acid Type

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.

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

2005 ◽  
Vol 102 (4) ◽  
pp. 783-792 ◽  
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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