Nonhalogenated Alkanes Cyclopropane and Butane Affect Neurotransmitter-gated Ion Channel and G-protein–coupled Receptors: Differential Actions on GABAA and Glycine Receptors

  title={Nonhalogenated Alkanes Cyclopropane and Butane Affect Neurotransmitter-gated Ion Channel and G-protein–coupled Receptors: Differential Actions on GABAA and Glycine Receptors},
  author={Koji Hara and Edmond I. Eger and Michael J. Laster and R. Adron Harris},
Background Anesthetic mechanisms of nonhalogenated alkanes cyclopropane and butane are not understood. This study was designed to look at which neurotransmitter receptors are possible targets for these anesthetics. Methods Effects of cyclopropane and butane on eight recombinant receptors expressed in Xenopus oocytes were examined electrophysiologically. To address molecular mechanisms of interaction with glycine and &ggr;-aminobutyric acid type A (GABAA) receptors, cyclopropane was further… 

Anesthetic synergy between two n-alkanes.

The Effects of Tramadol and Its Metabolite on Glycine, γ-Aminobutyric AcidA, and N-Methyl-d-Aspartate Receptors Expressed in Xenopus Oocytes

It is suggested that glycine receptors do not provide the antinociceptive effect of tramadol and that the inhibition of GABAA receptors at large concentration might correlate with convulsions.

The Effects of the Local Anesthetics Lidocaine and Procaine on Glycine and &ggr;-Aminobutyric Acid Receptors Expressed in Xenopus Oocytes

Lidocaine and procaine enhanced glycine receptor function at low concentrations and inhibited the functions of glycine and GABAA receptors at high concentrations, which may explain the pharmacological effects of LAs, such as antinociception and convulsion.

Effects of Anesthetics on Mutant N-Methyl-d-Aspartate Receptors Expressed in Xenopus Oocytes

Alcohols, inhaled anesthetics, and some injectable anesthetics inhibit the function of N-methyl-d-aspartate (NMDA) receptors, but the mechanisms responsible for this inhibition are not fully

Mutations M287L and Q266I in the Glycine Receptor &agr;1 Subunit Change Sensitivity to Volatile Anesthetics in Oocytes and Neurons, but Not the Minimal Alveolar Concentration in Knockin Mice

Results indicate that glycine receptors containing the &agr;1 subunit are not likely to be crucial for the action of isoflurane and other VAs.

Sites of alcohol and volatile anesthetic action on glycine receptors.

Hydrocarbon molar water solubility predicts NMDA vs. GABAA receptor modulation

Differences between unrelated receptor cut-off values suggest that the number, affinity, or efficacy of protein-hydrocarbon interactions at these sites likely differ.

Volatile Aromatic Anesthetics Variably Impact Human &ggr;-Aminobutyric Acid Type A Receptor Function

It is suggested that GABAA receptors contribute variably to the behavioral actions of volatile anesthetics and imply that the molecular determinants of anesthetic action on NMDA and GAB AA receptors are distinctly different.

Channel Gating of the Glycine Receptor Changes Accessibility to Residues Implicated in Receptor Potentiation by Alcohols and Anesthetics*

Conformational changes accompanying channel gating increase accessibility to amino acids critical for drug action in TM1, TM2, and TM3, which may provide a mechanism by which alcohols and anesthetics can act on glycine (and likely other) receptors.

&bgr;3-Containing Gamma-Aminobutyric AcidA Receptors Are Not Major Targets for the Amnesic and Immobilizing Actions of Isoflurane

If, relative to isoflurane, cyclopropane minimally increases GABA-induced chloride currents at any GABAA receptor subtype, the present data for MAC are consistent with the notion that GAB AA receptors do not mediate the immobility produced by inhaled anesthetics.



Nonhalogenated Alkane Anesthetics Fail to Potentiate Agonist Actions on Two Ligand-gated Ion Channels

The results suggest that the in vivo central nervous system depressant effects of nonhalogenated alkane anesthetics do not result from their abilities to potentiate agonist actions on ligand-gated ion channels.

The Anesthetic Mechanism of Urethane: The Effects on Neurotransmitter-Gated Ion Channels

At concentrations close to anesthetic 50% effective concentration, urethane had modest effects on all channels tested, suggesting the lack of a single predominant target for its action, which may account for its usefulness as a veterinary anesthetic.

Specific binding sites for alcohols and anesthetics on ligand-gated ion channels.

It is demonstrated that the anesthetic propanethiol covalently binds to cysteine residues introduced into a specific second transmembrane site in glycine receptor and gamma-aminobutyric acid type A receptor subunits and irreversibly enhances receptor function.

Enhancement of homomeric glycine receptor function by longchain alcohols and anaesthetics

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.

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

Observations support the idea that anaesthetics exert a specific effect on these ion-channel proteins, and allow for the future testing of specific hypotheses of the action of anaesthetic action.

Enhancement of Glycine Receptor Function by Ethanol Is Inversely Correlated with Molecular Volume at Position α267*

The results demonstrate that the size of the amino acid residue at position α267 plays a crucial role in determining the functional consequences of allosteric modulation of the Gly-R by alcohols.

Propofol and other intravenous anesthetics have sites of action on the gamma-aminobutyric acid type A receptor distinct from that for isoflurane.

The effects of propofol, etomidate, the barbiturate methohexital, and the steroid alphaxalone on wild-type and mutant GABAA receptors expressed in human embryonic kidney 293 cells indicate that the receptor structural requirements for positive modulation by volatile and intravenous general anesthetics may be quite distinct.

Effects of thiopental and its optical isomers on nicotinic acetylcholine receptors.

Both central neuronal and peripheral muscle nAChRs can be substantially inhibited by thiopental at surgical EC50 concentrations but with either no stereoselectivity or one opposite to that for general anesthesia.

Differential Effects of General Anesthetics on G Protein–coupled Inwardly Rectifying and Other Potassium Channels

Results of chimeric and multiple amino acid mutations suggest that the region containing the transmembrane domains, but not the pore-forming domain, may be involved in determining differences in anesthetic sensitivity between GIRK and IRK channels.

The interaction of general anaesthetics with recombinant GABAA and glycine receptors expressed in Xenopus laevis oocytes: a comparative study

The effects of binary combinations of pentobarbitone and propofol at maximally effective concentrations were mutually occlusive suggesting a common site, or mechanism, of action.