Modulation of Recombination Human γ-Aminobutyric Acid-A Receptors by Isoflurane 

1998 ◽  
Vol 88 (1) ◽  
pp. 206-217 ◽  
Author(s):  
George Lees ◽  
Michelle D. Edwards
Keyword(s):  
Physiological Role ◽  
Aminobutyric Acid ◽  
Maximal Response ◽  
Xenopus Laevis Oocytes ◽  
Gamma Aminobutyric Acid ◽  
Gaba A ◽  
Anesthetic Agents ◽  
Subunit Expression ◽  
Delta Subunit

Background The gamma-aminobutyric acid (GABA)A receptor/chloride channel has a broad-spectrum anesthetic sensitivity and is a key regulator of arousal. Each receptor/channel complex is an assembly of five protein subunits. Six subunit classes have been identified, each containing one to six members; many combinations are expressed throughout the brain. Benzodiazepines and intravenous anesthetic agents are clearly subunit dependent, but the literature to date suggests that volatile anesthetics are not. The physiological role of the delta subunit remains enigmatic, and it has not been examined as a determinant of anesthetic sensitivity. Methods Combinations of GABA(A) receptor subunit cDNAs were injected into Xenopus laevis oocytes: alpha1beta1, alpha1beta1gamma2L, alpha1beta1delta, and alpha1beta1gamma2Ldelta. Expression of functional ion channels with distinct signalling and pharmacologic properties was demonstrated within 1-4 days by established electrophysiological methods. Results Co-expression of the delta subunit produced changes in receptor affinity; current density; and the modulatory efficacy of diazepam, zinc, and lanthanum; it also produced subtle changes in the rate of desensitization in response to GABA. Isoflurane enhanced GABA-induced responses from all combinations: alphabeta delta (>10-fold) > alphabeta > alphabeta gamma > or = alphabeta gammadelta (approximately 5-fold). Dose-response plots were bell shaped. Compared with alphabeta gamma receptors (EC50 = 225 microM), both alphabeta delta (EC50 = 372 microM) and alphabeta gammadelta (EC50 = 399 microM) had a reduced affinity for isoflurane. Isoflurane (at a concentration close to the EC50 for each subunit) increased the affinity of GABA for its receptor but depressed the maximal response (alphabeta gamma and alphabeta gammadelta). In contrast, the small currents through alphabeta delta receptors were enhanced, even at saturating agonist concentrations. Conclusions Delta subunit expression alters GABA(A) receptor function but is not an absolute determinant of anesthetic sensitivity.

Regulation of endogenous dopamine release in amphibian retina by gamma-aminobutyric acid and glycine

1994 ◽  
Vol 11 (5) ◽  
pp. 1003-1012 ◽  
Author(s):  
Jeffrey H. Boatright ◽  
Nara M. Rubim ◽  
P. Michael Iuvone
Keyword(s):  
Receptor Agonist ◽  
Dopamine Release ◽  
Receptor Activation ◽  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Gaba A ◽  
Endogenous Dopamine ◽  
Endogenous Dopamine Release ◽  
Inhibitory Tone

AbstractEndogenous dopamine release in the retina of the African clawed frog (Xenopus laevis) increases in light and decreases in darkness. The roles of the inhibitory amino acid transmitters gamma-aminobutyric acid (GABA) and glycine in regulating this light/dark difference in dopamine release were explored in the present study. Exogenous GABA, the GABA-A receptor agonist muscimol, the GABA-B receptor agonist baclofen, and the GABA-C receptor agonist cis-aminocrotonic acid (CACA) suppressed light-evoked dopamine overflow from eyecups. The effects of GABA-A and -B receptor agonists were selectively reversed by their respective receptor-specific antagonists, whereas the effect of CACA was reversed by the competitive GABA-A receptor antagonist bicuculline. The benzodiazepine diazepam enhanced the effect of muscimol on light-evoked dopamine release. Both GABA-A and -B receptor antagonists stimulated dopamine release in light or darkness. Bicuculline was more potent in light than in darkness. These data suggest that retinal dopaminergic neurons are inhibited by GABA-A and -B receptor activation in both light and darkness but that GABA-mediated inhibitory tone may be greater in darkness than in light.Exogenous glycine inhibited light-stimulated dopamine release in a concentration-dependent and strychnine-sensitive manner. However, strychnine alone did not increase dopamine release in light or darkness, nor did it augment bicuculline-stimulated release in darkness. Additionally, both strychnine and 7-chlorokynurenate, an antagonist of the strychnine-insensitive glycine-binding site of the N-methyl-D-aspartate subtype of glutamate receptor, suppressed light-evoked dopamine release. Thus, the role of endogenous glycine in the regulation of dopamine release remains unclear.

Gamma-aminobutyric acid (GABA): a para- and/or autocrine hormone in the pituitary

2001 ◽  
Vol 15 (6) ◽  
pp. 1089-1091 ◽  
Author(s):  
ARTUR MAYERHOFER ◽  
BARBARA HÖHNE-ZELL ◽  
KATIA GAMEL-DIDELON ◽  
HEIKE JUNG ◽  
PETER REDECKER ◽  
...  
Keyword(s):  
Aminobutyric Acid ◽  
Gamma Aminobutyric Acid ◽  
Gaba A

Changes in gamma-aminobutyric acid and somatostatin in epileptic cortex associated with low-grade gliomas

1992 ◽  
Vol 77 (2) ◽  
pp. 209-216 ◽  
Author(s):  
Michael M. Haglund ◽  
Mitchel S. Berger ◽  
Dennis D. Kunkel ◽  
JoAnn E. Franck ◽  
Saadi Ghatan ◽  
...  
Keyword(s):  
Epileptiform Activity ◽  
Aminobutyric Acid ◽  
Low Grade ◽  
Tumor Infiltration ◽  
Gamma Aminobutyric Acid ◽  
Content Type ◽  
Low Grade Gliomas ◽  
Neuronal Populations ◽  
Significant Difference

✓ The role of specific neuronal populations in epileptic foci was studied by comparing epileptic and nonepileptic cortex removed from patients with low-grade gliomas. Epileptic and nearby (within 1 to 2 cm) nonepileptic temporal lobe neocortex was identified using electrocorticography. Cortical specimens taken from four patients identified as epileptic and nonepileptic were all void of tumor infiltration. Somatostatin- and γ-aminobutyric acid (GABAergic)-immunoreactive neurons were identified and counted. Although there was no significant difference in the overall cell count, the authors found a significant decrease in both somatostatin- and GABAergic-immunoreactive neurons (74% and 51 %, respectively) in the epileptic cortex compared to that in nonepileptic cortex from the same patient. It is suggested that these findings demonstrate changes in neuronal subpopulations that may account for the onset and propagation of epileptiform activity in patients with low-grade gliomas.

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.

Brain amino acid concentrations during diving and acid-base stress in turtles

1985 ◽  
Vol 58 (6) ◽  
pp. 1751-1754 ◽  
Author(s):  
B. M. Hitzig ◽  
M. P. Kneussl ◽  
V. Shih ◽  
R. D. Brandstetter ◽  
H. Kazemi
Keyword(s):  
Amino Acid ◽  
Aminobutyric Acid ◽  
Breath Hold ◽  
Gamma Aminobutyric Acid ◽  
Amino Acid Neurotransmitters ◽  
Acid Base ◽  
Ventilatory Drive ◽  
Amino Acid Concentrations ◽  
Brain Amino Acid

To assess the role of brain amino acid neurotransmitters in the breath hold of diving animals, concentrations of free amino acids present in the brains of turtles immediately after 2 h of apneic diving (at 20 degrees C) were measured. Additionally, the same measurements were performed on four other groups of animals subjected to 2 h of hypercapnia (8% CO2 in air), anoxia (N2 breathing), anoxia plus hypercapnia (8% CO2–92% N2), or air breathing (control). Significant changes in the concentrations of the inhibitory amino acid neurotransmitters known to affect respiration [gamma-aminobutyric acid (GABA) and taurine] were seen. GABA increased significantly in those animals subjected to anoxia, whereas taurine decreased significantly in the diving animals and increased significantly in those subjected to anoxia plus hypercapnia. These results suggest that the attenuated central ventilatory drive during diving in these animals may be related to alterations in brain concentrations of GABA and taurine.

scholarly journals HPLC-Based Activity Profiling for GABAA Receptor Modulators in Murraya exotica

2019 ◽  
Vol 14 (1) ◽  
pp. 1934578X1901400
Author(s):  
Nova Syafni ◽  
Fahimeh Moradi-Afrapoli ◽  
Ombeline Danton ◽  
Anke Wilhelm ◽  
Marco Stadler ◽  
...  
Keyword(s):  
Gaba Receptors ◽  
Xenopus Oocyte ◽  
Aminobutyric Acid ◽  
Xenopus Laevis Oocytes ◽  
Gamma Aminobutyric Acid ◽  
Activity Assay ◽  
Chloride Currents ◽  
Activity Profiling ◽  
Murraya Exotica ◽  
Receptor Modulators

A dichloromethane extract from twigs and leaves of Murraya exotica produced allosteric potentiation of gamma aminobutyric acid (GABA) induced chloride currents in a microelectrode assay in Xenopus laevis oocytes expressing GABA receptors of α1, β2, γ2s subunit composition. The activity was tracked by HPLC-based activity profiling utilizing a zebrafish locomotor activity assay. Osthol (9) was identified as the main active compound. In addition, five other coumarins and four flavonols were identified. Osthol (9) and structurally related coumurrayin (10) were tested in the Xenopus oocyte assay. Compound 9 potentiated GABAA-induced chloride currents by 487 ± 42%, with an EC50 of 46 ± 10 μM, while 10 showed negligible effects on chloride currents. In silico evaluation of physicochemical properties showed that 9 and 10 had properties that are favorable for oral bioavailability and BBB permeability.

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