Determination of Halothane in Gas, Blood, and Tissues by Chemical Extraction and Gas Chromatography

Allott, P.R.; Steward, A.; Mapleson, W.W.

doi:10.1093/bja/43.10.913

Cited by 30 publications

(11 citation statements)

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“…Anesthetic concentration within the chamber was determined using a Capnomac Ultima analyzer (Datex Engostrom). Yeast medium/gas partition coefficients for halothane, isoflurane, and sevoflurane at 30°C were determined by gas chromatography (Hewlett Packard 5890 series II plus) using the method previously described (35). Concentration of each anesthetic in the medium was thus calculated in millimolar units.…”

Section: Methodsmentioning

confidence: 99%

Synaptic PDZ Domain-mediated Protein Interactions Are Disrupted by Inhalational Anesthetics

Fang

Tao

et al. 2003

Journal of Biological Chemistry

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Anesthetics exert multiple effects on the central nervous system through altering synaptic transmission, but the mechanisms for this process are poorly understood. PDZ domain-mediated protein interactions play a central role in organizing signaling complexes around synaptic receptors for efficient signal transduction. We report here that clinically relevant concentrations of inhalational anesthetics dose-dependently and specifically inhibit the PDZ domain-mediated protein interaction between PSD-95 or PSD-93 and the N-methyl-Daspartate receptor or neuronal nitric-oxide synthase. These inhibitory effects are immediate, potent, and reversible and occur at a hydrophobic peptide-binding groove on the surface of the second PDZ domain of PSD-95 in a manner relevant to anesthetic action. These findings reveal the PDZ domain as a new molecular target for inhalational anesthetics.Inhalational anesthetics have been in widespread use for more than 150 years and have been essential in the development of modern surgical procedures, but their molecular mechanisms have remained poorly understood. Early hypotheses based on nonspecific interactions of lipid-soluble anesthetics with the lipid bilayer of neuronal membranes have largely given way to the recent suggestion that anesthetics interact with multiple membrane-associated proteins involved in synaptic transmission (1-5). Inhibitory GABA A and glycine receptors and excitatory N-methyl-D-aspartate (NMDA), 1 nicotinic acetylcholine, and serotonin receptors have been demonstrated as possible physiological targets that underlie general anesthesia (6). Inhalational anesthetics have been shown to both enhance inhibitory receptor-mediated synaptic neurotransmission and depress excitatory receptor-mediated synaptic neurotransmission.Recent studies have revealed a much more complicated picture of excitatory receptor-mediated synaptic transmission than previously anticipated. For efficient synaptic transmission, the downstream effectors are targeted to the receptors by scaffolding proteins via a complex network of protein-protein interactions (7). The PDZ domain is one of the most common protein-protein recognition modules that have been found in diverse scaffolding and signaling proteins (8, 9). The name PDZ derives from the first three proteins (PSD-95/SAP90, Dlg, and ZO-1 (10)) in which these domains were identified. The PDZ domain recognizes specific C-terminal motifs found in target proteins, most often in the cytoplasmic tails of transmembrane receptors and channels (10, 11). The PDZ domain can also recognize structure-related internal motifs to form homo-and heteromeric PDZ-PDZ interactions (12-15). Therefore, PDZ domain-mediated protein-protein interactions provide a framework for the assembly of multiprotein signaling complexes at synapses and neuromuscular junctions. These interactions coordinate and guide the flow of regulatory information and regulate receptor and ion channel activities (16 -19).One of the best understood PDZ domain proteins at synapses is PSD-95, a modula...

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Section: Methodsmentioning

confidence: 99%

Synaptic PDZ Domain-mediated Protein Interactions Are Disrupted by Inhalational Anesthetics

Fang

Tao

et al. 2003

Journal of Biological Chemistry

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“…Concentrations of halothane and trichloroethylene in the various Gey's solutions were measured by gas chromatography following an extraction procedure. Halothane concentrations were obtained by the method of Allott, Steward and Mapleson (1971). Trichloroethylene was analysed following extraction into carbon disulphide, using toluene as an internal standard.…”

Section: Analysis By Gas Chromatographymentioning

confidence: 99%

Inhibition, by Anaesthetic Agents, of Human Leucocyte Locomotion Towards Chemical Attractants

Moudgil

Allan

Russell

et al. 1977

British Journal of Anaesthesia

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The effects of local, i.v. and volatile anaesthetic agents on locomotion of human blood leucocytes were studied in vitro. Blood neutrohpils and monocytes and PHA-activated lymphocytes were allowed to migrate in filters towards standard chemotactic agents and the effect of adding anaesthetic agents to the system was measured. The results showed that locomotion of all cell types was depressed reversibly by all classes of anaesthetics used at clinical concentrations. The pattern of depression varied according to the cell type under study and the class of anaesthetic used. The action of anaesthetics on chemically stimulated locomotion of leucocytes was analysed. It was concluded that the principal action of these drugs is primarily on the mechanism of locomotion itself, rather than on the capacity of the cells to detect and respond to concentration gradients of attractants. Serum albumin can protect against the inhibitory action of anaesthetics.

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“…Protein-protein interactions were evaluated as described in our previous study 18 by growth of yeast on selective agar plates sealed in incubator chambers containing different concentrations of isoflurane, which was introduced into the chambers by its conventional calibrated anesthesia vaporizer (OHIO Medical Co., Gurnee, IL) for 30 min of equilibrium with air at 3 l/min. Anesthetic concentration within the chamber was determined with a Capnomac Ultima analyzer (Datex-Engstrom, Helsinki, Finland), and the yeast medium/gas partition coefficient for isoflurane at 30°C was determined by gas chromatography (Hewlett Packard 5890 series II plus, Agilent Technologies, Inc., Santa Clara, CA) according to the method described previously 18;21 . Concentration of halothane or isoflurane in the medium was calculated in millimolar units.…”

Section: Methodsmentioning

confidence: 99%

Inhalational Anesthetics Disrupt Postsynaptic Density Protein-95, Drosophila Disc Large Tumor Suppressor, and Zonula Occludens-1 Domain Protein Interactions Critical to Action of Several Excitatory Receptor Channels Related to Anesthesia

et al. 2015

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Background We have shown previously that inhaled anesthetics disrupt the interaction between the second postsynaptic density protein-95, Drosophila disc large tumor suppressor, and zonula occludens-1 (PDZ) domain of postsynaptic density protein-95 (PSD-95) and the C-terminus of N-methyl-D-aspartate receptor subunits NR2A and NR2B. Our data indicate that PDZ domains may serve as a molecular target for inhaled anesthetics. However, the underlying molecular mechanisms remain to be illustrated. Methods Glutathione S-transferase pull-down assay, co-immunoprecipitation and yeast two-hybrid analysis were used to assess PDZ domain-mediated protein-protein interactions in different conditions. Nuclear magnetic resonance spectroscopy was used to investigate isoflurane-induced chemical shift changes in the PDZ1–3 domains of PSD-95. A surface plasmon resonance-based BIAcore assay was used to examine the ability of isoflurane to inhibit the PDZ domain-mediated protein-protein interactions in real time. Results Halothane and isoflurane dose dependently inhibited PDZ domain-mediated interactions between PSD-95 and Shaker-type potassium channel Kv1.4 and between α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid receptor subunit GluA2 and its interacting proteins— glutamate receptor interacting protein or protein interacting with c kinase 1. However, halothane and isoflurane had no effect on PDZ domain-mediated interactions between γ-aminobutyric acid, type B receptor and its interacting proteins. The inhaled anesthetic isoflurane mostly affected the residues close to or in the peptide binding groove of PSD-95 PDZ1 and PDZ2 (especially PDZ2), while barely affecting the peptide binding groove of PSD-95 PDZ3. Conclusion These results suggest that inhaled anesthetics interfere with PDZ domain-mediated protein-protein interactions at several receptors important to neuronal excitation, anesthesia and pain processing.

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Determination of Halothane in Gas, Blood, and Tissues by Chemical Extraction and Gas Chromatography

Cited by 30 publications

References 0 publications

Synaptic PDZ Domain-mediated Protein Interactions Are Disrupted by Inhalational Anesthetics

Synaptic PDZ Domain-mediated Protein Interactions Are Disrupted by Inhalational Anesthetics

Inhibition, by Anaesthetic Agents, of Human Leucocyte Locomotion Towards Chemical Attractants

Inhalational Anesthetics Disrupt Postsynaptic Density Protein-95, Drosophila Disc Large Tumor Suppressor, and Zonula Occludens-1 Domain Protein Interactions Critical to Action of Several Excitatory Receptor Channels Related to Anesthesia

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