Abstract
The interaction of three volatile general anaesthetics (halothane, enflurane and methoxyflurane) with erythrocyte membranes at concentrations causing protection of intact erythrocytes against hypotonic lysis was investigated in the hope of deriving fundamental information regarding the membrane perturbational characteristics of these substances as compared with those of local anaesthetics studied previously. The volatile agents increased the susceptibility of membrane proteins and, to a somewhat lesser extent, of phospholipids to trinitrophenylation by picryl chloride or trinitrobenzenesulfonic acid but decreased the accessibility of membrane protein sulfhydryl groups to modification by 5, 5’-dithio-bis-(2-nitrobenzoic acid). These observations stood in marked contrast to our previous findings with local anaesthetics, in that these substances, when compared to general anaesthetics at concentrations producing equivalent erythrocyte stabilization, caused a greater enhancement of trinitrophenylation, largely restricted to the phospholipid component and an increased exposure of membrane sulfhydryl groups. Further evidence for alterations in membrane proteins produced by concentrations of volatile anaesthetics relevant to surgical anaesthesia was obtained from the observation that all three agents produced significant decreases in the activation energy of membrane-bound p-nitrophenylphosphatases. Preliminary experiments with brain synaptic membranes suggested that the structural and functional consequences of membrane-anaesthetic interaction in erythrocytes are relevant to the situation in excitable tissues. Our results indicate, therefore, that general and local anaesthetics cause distinctly different alterations in the properties of model membrane systems and this may reflect corresponding differences in the molecular mechanisms by which these groups of agents produce their anaesthetic actions.
Résumé
L’interaction de trois anesthesiques volatils (halothane, enflurane et méthoxyflurane) avec la membrane érythrocytaire utilisés à des concentrations qui protegènt les érythrocytes intacts contre la lyse hypotonique a été étudiée avec l’espoir d’obtenir des renseignements fondamentaux sur les perturbations caractéristiques que causent ces substances lorsqu’on les compare aux anesthesiques locaux. Les agents anesthésiques volatils ont augmenté la susceptibilité des protéines de la membrane et, à un degré moindre, des phospholipides à la trinitrophénylation par le chlorure de picryl ou l’acide trinitrobenzènesulfonique mais a diminué l’accessibilité des groupes protéiques sulfhydryl de la membrane à la modification apportée par l’acide 5,5’-dithio-bis-(2-nitrebonzoïque). Ces observations contrastaient fortement avec nos données précédentes concernant les anesthésiques locaux par le fait que lorsque ces substances étaient comparées aux anesthésiques généraux à des concentrations qui produisaient une stabilisation érythrocytaire équivalente, elles causaient une augmentation plus marquée de la trinitrophénylation, intéressant plus spécialement le compose phospholipidique et une augmentation de I’exposition du groupe sulfhydryl de la membrane. Une évidence additionnelle démontrant les altérations des protéines de la membrane produites par des concentrations d’anésthesiques volatils identiques à celles que l’on emploie en anesthésie chirurgicale fut obtenue lorsqu’on a observé que les trois agents produisaient une baisse significative de I’activation de l’énergie des p-nitrophénylphosphatases liées a la membrane. Une étude préliminaire faite avec des membranes post-synaptiques du cerveau porte à croire que les Consequénces structurelles et fonctionnelles de l’interaction anesthésique sur la membrane érythrocytaire peuvent être identiques à celles qui surviennent dans les tissus excitables. Nos données indiquent done que les agents anesthésiques locaux et généraux causent des altérations distinctes sur les propriétés des membranes et que ceci peut se réfléter par des différences correspondantes sur les mécanismes moléculaires d’action des différents groupes d’agents anesthésiques.
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Godin, D.V., Vicario, G.D. Molecular aspects of inhalational anaesthetic interaction with excitable and non-excitable membranes. Canad. Anaesth. Soc. J. 28, 201–209 (1981). https://doi.org/10.1007/BF03005501
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DOI: https://doi.org/10.1007/BF03005501