Faculty Opinions recommendation of Effect of isoflurane and other potent inhaled anesthetics on minimum alveolar concentration, learning, and the righting reflex in mice engineered to express alpha1 gamma-aminobutyric acid type A receptors unresponsive to isoflurane.

2007 ◽  
Author(s):  
Douglas Raines
Keyword(s):  
Minimum Alveolar Concentration ◽  
Type A ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Inhaled Anesthetics ◽  
Acid Type ◽  
Righting Reflex

scholarly journals Methoxycarbonyl-etomidate

2009 ◽  
Vol 111 (2) ◽  
pp. 240-249 ◽  
Author(s):  
Joseph F. Cotten ◽  
S Shaukat Husain ◽  
Stuart A. Forman ◽  
Keith W. Miller ◽  
Elizabeth W. Kelly ◽  
...  
Keyword(s):  
Half Life ◽  
Human Liver ◽  
Type A ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Loss Of Righting Reflex ◽  
Acid Type ◽  
Righting Reflex ◽  
S9 Fraction

Background Etomidate is a rapidly acting sedative-hypnotic that provides hemodynamic stability. It causes prolonged suppression of adrenocortical steroid synthesis; therefore, its clinical utility and safety are limited. The authors describe the results of studies to define the pharmacology of (R)-3-methoxy-3-oxopropyl1-(1-phenylethyl)-1H-imidazole-5-carboxylate (MOC-etomidate), the first etomidate analogue designed to be susceptible to ultra-rapid metabolism. Methods The gamma-aminobutyric acid type A receptor activities of MOC-etomidate and etomidate were compared by using electrophysiological techniques in human alpha1beta2gamma2l receptors. MOC-etomidate's hypnotic concentration was determined in tadpoles by using a loss of righting reflex assay. Its in vitro metabolic half-life was measured in human liver S9 fraction, and the resulting metabolite was provisionally identified by using high-performance liquid chromatography/mass spectrometry techniques. The hypnotic and hemodynamic actions of MOC-etomidate, etomidate, and propofol were defined in rats. The abilities of MOC-etomidate and etomidate to inhibit corticosterone production were assessed in rats. Results MOC-etomidate potently enhanced gamma-aminobutyric acid type A receptor function and produced loss of righting reflex in tadpoles. Metabolism in human liver S9 fraction was first-order, with an in vitro half-life of 4.4 min versus more than 40 min for etomidate. MOC-etomidate's only detectable metabolite was a carboxylic acid. In rats, MOC-etomidate produced rapid loss of righting reflex that was extremely brief and caused minimal hemodynamic changes. Unlike etomidate, MOC-etomidate produced no adrenocortical suppression 30 min after administration. Conclusions MOC-etomidate is an etomidate analogue that retains etomidate's important favorable pharmacological properties. However, it is rapidly metabolized, ultra-short-acting, and does not produce prolonged adrenocortical suppression after bolus administration.

Effect of Isoflurane and Other Potent Inhaled Anesthetics on Minimum Alveolar Concentration, Learning, and the Righting Reflex in Mice Engineered to Express α1γ-Aminobutyric Acid Type A Receptors Unresponsive to Isoflurane

2007 ◽  
Vol 106 (1) ◽  
pp. 107-113 ◽  
Author(s):  
James M. Sonner ◽  
David F. Werner ◽  
Frank P. Elsen ◽  
Yilei Xing ◽  
Mark Liao ◽  
...  
Keyword(s):  
Fear Conditioning ◽  
Minimum Alveolar Concentration ◽  
Hippocampal Slices ◽  
Type A ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Wild Type ◽  
Inhibitory Postsynaptic Currents ◽  
Postsynaptic Currents ◽  
Acid Type

Background Enhancement of the function of gamma-aminobutyric acid type A receptors containing the alpha1 subunit may underlie a portion of inhaled anesthetic action. To test this, the authors created gene knock-in mice harboring mutations that render the receptors insensitive to isoflurane while preserving sensitivity to halothane. Methods The authors recorded miniature inhibitory synaptic currents in hippocampal neurons from hippocampal slices from knock-in and wild-type mice. They also determined the minimum alveolar concentration (MAC), and the concentration at which 50% of animals lost their righting reflexes and which suppressed pavlovian fear conditioning to tone and context in both genotypes. Results Miniature inhibitory postsynaptic currents decayed more rapidly in interneurons and CA1 pyramidal cells from the knock-in mice compared with wild-type animals. Isoflurane (0.5-1 MAC) prolonged the decay phase of miniature inhibitory postsynaptic currents in neurons of the wild-type mice, but this effect was significantly reduced in neurons from knock-in mice. Halothane (1 MAC) slowed the decay of miniature inhibitory postsynaptic current in both genotypes. The homozygous knock-in mice were more resistant than wild-type controls to loss of righting reflexes induced by isoflurane and enflurane, but not to halothane. The MAC for isoflurane, desflurane, and halothane did not differ between knock-in and wild-type mice. The knock-in mice and wild-type mice did not differ in their sensitivity to isoflurane for fear conditioning. Conclusions gamma-Aminobutyric acid type A receptors containing the alpha1 subunit participate in the inhibition of the righting reflexes by isoflurane and enflurane. They are not, however, involved in the amnestic effect of isoflurane or immobilizing actions of inhaled agents.

[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.

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