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Assessing Changes in Volatile General Anesthetic Sensitivity of Mice after Local or Systemic Pharmacological Intervention
Published on: October 16, 2013
Perturbations of model protein systems as a basis for the central and peripheral mechanisms of general anaesthesia
Abstract:
Protein perturbations associated with anaesthetic interactions are relevant to: (a) the central molecular mechanisms of general anaesthesia; (b) the molecular basis of physiological selectivity and anaesthetic specificity of the many 'side-effects' of anaesthesia; (c) the use of anaesthetic agents as selective hydrophobic probes for the study of protein structures and activities in detail. Small but specific protein perturbations have been studied with various nuclear magnetic resonance procedures with haemoglobin as a model protein to establish the 'ground-rules' for anaesthetic-macromolecule interactions. The correlation of one aspect of these perturbations with anaesthetic potency and hydrophobic solubility indicates that hydrophobic pockets in proteins can behave like bulk-lipid phases in terms of their solubility characteristics. Other aspects appear to depend on physical characteristics such as size, geometry, structure and composition of the individual agents. These data support the hypothesis that anaesthetic actions can be explained on a molecular basis by direct interactions with proteins in addition to lipid and aqueous effects.
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