Crystallographic Studies with Xenon and Nitrous Oxide Provide Evidence for Protein-dependent Processes in the Mechanisms of General Anesthesia
| Autor: | Hélène N. David, Nathalie Colloc'h, G. Marassio, Thierry Prangé, Jacques H. Abraini, Beatrice Vallone |
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| Přispěvatelé: | Université de Caen Normandie ( UNICAEN ), Normandie Université ( NU ), Institut de Recherches Biomédicales des Armées, Departement d'anesthésiologie, Faculté de médecine de l'Université Laval (Québec) [Canada], Centre de recherche Hotel-Dieu de Lévis, Lévis QC, Canada, Istituto di Biologia e Patologia Molecolari, CNR, and Dipartimento di Scienze Biochimiche, Università degli Studi di Roma 'La Sapienza', Laboratoire de cristallographie et RMN biologiques ( LCRB - UMR 8015 ), Université Paris Descartes - Paris 5 ( UPD5 ) -Centre National de la Recherche Scientifique ( CNRS ), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales ( ISTCT ), Normandie Université ( NU ) -Normandie Université ( NU ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Centre National de la Recherche Scientifique ( CNRS ), Université de Caen Normandie (UNICAEN), Normandie Université (NU), Faculté de médecine de l'Université Laval [Québec] (ULaval), Université Laval [Québec] (ULaval)-Université Laval [Québec] (ULaval), CNR Istituto di Biologia e Patologia Molecolari [Roma] (CNR | IBPM), National Research Council of Italy | Consiglio Nazionale delle Ricerche (CNR), Laboratoire de cristallographie et RMN biologiques (LCRB - UMR 8015), Université Paris Descartes - Paris 5 (UPD5)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS), Imagerie et Stratégies Thérapeutiques des pathologies Cérébrales et Tumorales (ISTCT), Normandie Université (NU)-Normandie Université (NU)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Università degli Studi di Roma 'La Sapienza' = Sapienza University [Rome], Normandie Université (NU)-Normandie Université (NU)-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA), Università degli Studi di Roma 'La Sapienza' [Rome], Centre National de la Recherche Scientifique (CNRS)-Université Paris Descartes - Paris 5 (UPD5) |
| Jazyk: | angličtina |
| Rok vydání: | 2014 |
| Předmět: |
inorganic chemicals
Xenon General anesthetics Urate Oxidase [SDV]Life Sciences [q-bio] Receptors Drug Nitrous Oxide chemistry.chemical_element Neuroglobin Nerve Tissue Proteins Anesthesia General Crystallography X-Ray chemistry.chemical_compound xenon protein crystallography Medicine Animals ComputingMilieux_MISCELLANEOUS Binding Sites [ SDV ] Life Sciences [q-bio] business.industry Myoglobin Oxygen transport Proteins Nitrous oxide Globins Crystallography Anesthesiology and Pain Medicine chemistry Anesthesia Anesthetics Inhalation Muramidase business |
| Zdroj: | Anesthesiology Anesthesiology, Lippincott, Williams & Wilkins, 2014, 121 (5), pp.1018-1027. 〈10.1097/ALN.0000000000000435〉 Anesthesiology, 2014, 121 (5), pp.1018-1027. ⟨10.1097/ALN.0000000000000435⟩ Anesthesiology, Lippincott, Williams & Wilkins, 2014, 121 (5), pp.1018-1027. ⟨10.1097/ALN.0000000000000435⟩ |
| ISSN: | 0003-3022 |
| DOI: | 10.1097/ALN.0000000000000435〉 |
| Popis: | Background: The mechanisms by which general anesthetics, including xenon and nitrous oxide, act are only beginning to be discovered. However, structural approaches revealed weak but specific protein–gas interactions. Methods: To improve knowledge, we performed x-ray crystallography studies under xenon and nitrous oxide pressure in a series of 10 binding sites within four proteins. Results: Whatever the pressure, we show (1) hydrophobicity of the gas binding sites has a screening effect on xenon and nitrous oxide binding, with a threshold value of 83% beyond which and below which xenon and nitrous oxide, respectively, binds to their sites preferentially compared to each other; (2) xenon and nitrous oxide occupancies are significantly correlated respectively to the product and the ratio of hydrophobicity by volume, indicating that hydrophobicity and volume are binding parameters that complement and oppose each other’s effects; and (3) the ratio of occupancy of xenon to nitrous oxide is significantly correlated to hydrophobicity of their binding sites. Conclusions: These data demonstrate that xenon and nitrous oxide obey different binding mechanisms, a finding that argues against all unitary hypotheses of narcosis and anesthesia, and indicate that the Meyer–Overton rule of a high correlation between anesthetic potency and solubility in lipids of general anesthetics is often overinterpreted. This study provides evidence that the mechanisms of gas binding to proteins and therefore of general anesthesia should be considered as the result of a fully reversible interaction between a drug ligand and a receptor as this occurs in classical pharmacology. |
| Databáze: | OpenAIRE |
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