Sites of alcohol and volatile anaesthetic action on GABAA and glycine receptors

@article{Mihic1997SitesOA,
  title={Sites of alcohol and volatile anaesthetic action on GABAA and glycine receptors},
  author={S John Mihic and Qing Ye and Marilee J. Wick and Vladimir V. Koltchine and Matthew David Krasowski and Suzanne E. Finn and Maria Paola Mascia and C F Valenzuela and Kirsten K. Hanson and Eric P. Greenblatt and R. Adron Harris and Neil L. Harrison},
  journal={Nature},
  year={1997},
  volume={389},
  pages={385-389}
}
Volatile anaesthetics have historically been considered to act in a nonspecific manner on the central nervous system. More recent studies, however, have revealed that the receptors for inhibitory neurotransmitters such as γ-aminobutyric acid (GABA) and glycine are sensitive to clinically relevant concentrations of inhaled anaesthetics. The function of GABAA and glycine receptors is enhanced by a number of anaesthetics and alcohols, whereas activity of the related GABA ρ1 receptor is reduced. We… 
Shared structural mechanisms of general anesthetics and benzodiazepines
TLDR
Cryo-electron microscopy structures of GABA A receptors bound to intravenous anaesthetic and benzodiazepines reveal both common and distinct transmembrane binding sites, and show that the mechanisms of action of anaesthetics partially overlap with those of benzodiazines.
Allosteric Modulation of GABAA Receptor Function by General Anesthetics and Alcohols
TLDR
A review of recent work which utilizes recombinant chimeric and mutated receptors to identify regions of the GABAA receptors that are important for the modulatory actions of general anesthetics and alcohols on γ-aminobutyric acidA (GABAA) receptors.
Sites of Volatile Anesthetic Action on Kainate (Glutamate Receptor 6) Receptors*
TLDR
It is suggested that a specific amino acid, Gly-819, is critical for the action of volatile anesthetics, but not of ethanol or pentobarbital, on the GluR6 receptor.
Divergence of Volatile Anesthetic Effects in Inhibitory Neurotransmitter Receptors
TLDR
The results support the involvement of multiple protein domains in the mechanism of VA modulation of GABA and glycine receptors and show, for the first time, functional divergence of VA action on a single protein target.
Antagonism of Inhalant and Volatile Anesthetic Enhancement of Glycine Receptor Function*
TLDR
A mutant glycine receptor, insensitive to the enhancing effects of ethanol but not anesthetics or inhalants, demonstrated antagonism of anesthetic and inhalant effects on this receptor, suggesting the existence of overlapping molecular sites of action for ethanol, inhalant, and volatileAnesthetics on glycine receptors.
Effects of Isoflurane on &ggr;-Aminobutyric Acid Type A Receptors Activated by Full and Partial Agonists
TLDR
The results suggest that the volatile anesthetic isoflurane exerts at least some of its effects on the GABAA receptor via alterations in gating rather than simply changing binding or unbinding of the agonist.
Regulation of GABAA receptors by prolonged exposure to endogenous and exogenous ligands
Sites of alcohol and volatile anesthetic action on glycine receptors.
...
1
2
3
4
5
...

References

SHOWING 1-10 OF 27 REFERENCES
Inhibition of rho1 receptor GABAergic currents by alcohols and volatile anesthetics.
  • S. Mihic, R. Harris
  • Biology
    The Journal of pharmacology and experimental therapeutics
  • 1996
TLDR
The opposite effects of alcohols and anesthetics on rho1 and GABA(A) receptors, despite their significant amino acid sequence homology, may help in the identification of the particular amino acids responsible for the actions of these compounds on these receptors.
Modulation of the GABAA receptor by propofol is independent of the gamma subunit.
TLDR
It is concluded that the gamma 2 subunit is not a prerequisite for activation of GABAA receptors by propofol or for its potentiation of GABA-activated currents, but the subunit may contribute to the efficacy of prop ofol as a GAB AA receptor activator.
General anesthetics potentiate gamma-aminobutyric acid actions on gamma-aminobutyric acidA receptors expressed by Xenopus oocytes: lack of involvement of intracellular calcium.
TLDR
It is found that diverse anesthetics potentiate GABA-induced Cl- currents, but this action is not mediated by a release of intracellular Ca++, suggesting that the Ca(++)-dependent Cl- current was not activated by these anesthetic per se.
Actions of long chain alcohols on GABAa and glutamate receptors: relation to in vivo effects
TLDR
The in vivo effects of long chain alcohols are not likely to be due to their actions on NMDA, AMPA, or kainate receptors, but may be due instead to potentiation of GABAA receptor function.
Positive modulation of human gamma-aminobutyric acid type A and glycine receptors by the inhalation anesthetic isoflurane.
TLDR
The results show that not all ligand-gated chloride channel receptors are sensitive to isoflurane and, therefore, that the anesthetic interacts with specific structural determinants of these ion channel proteins.
Ethanol inhibition of nicotinic acetylcholine type alpha 7 receptors involves the amino-terminal domain of the receptor.
TLDR
Ethanol was found to inhibit the function of this chimeric receptor in a manner similar to that of nACh alpha 7 receptors, suggesting that the amino-terminal domain of the receptor is involved in the inhibition.
Enhancement of homomeric glycine receptor function by longchain alcohols and anaesthetics
TLDR
The results suggest that the α subunits of strychnine‐sensitive glycine receptors contain sites of action for n‐alcohols, propofol, alphaxalone, pentobarbitone and volatile anaesthetics, but not for ketamine and etomidate.
A discrete site for general anesthetics on a postsynaptic receptor.
TLDR
It is found that specific mutations in the acetylcholine receptor pore-forming M2 domains enhance the sensitivity of the receptor to the general anesthetics isoflurane, hexanol, and octanol, suggesting that these agents act by binding directly to a discrete protein site at or near these residues.
...
1
2
3
...