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Enhancement of homomeric glycine receptor function by longchain alcohols and anaesthetics
Author(s) -
Mascia Maria Paola,
Machu Tina K.,
Harris R. Adron
Publication year - 1996
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1996.tb16042.x
Subject(s) - homomeric , chemistry , glycine receptor , glycine , pharmacology , receptor , strychnine , stereochemistry , biophysics , biochemistry , amino acid , protein subunit , medicine , biology , gene
1 The effects of n‐alcohols (ethanol to dodecanol) and anaesthetics on strychnine‐sensitive glycine receptors were studied in Xenopus oocytes expressing homomeric α1 or α2 glycine receptor subunits, with the two electrode voltage‐clamp recording technique. 2 The glycine‐induced chloride conductance of homomeric α glycine receptors was potentiated by all the alcohols tested when an EC 2 concentration of glycine was used. Homomeric α1 and α2 receptors were potentiated similarly by the n‐alcohols, except that low concentrations of ethanol produced greater potentiation with α1, as previously reported. 3 Increasing the n‐alcohol carbon number has been shown to increase the potency of the alcohols up to decanol at concentrations corresponding to EC 50 s for producing loss of righting reflex in tadpoles. However, dodecanol was no more potent than decanol, and only modest potentiation (30–60%) was obtained with dodecanol, in contrast to marked (150–200%) potentiation with the other alcohols. Thus, a ‘cut‐off’ occurred at about dodecanol. 4 Propofol, alphaxalone, pentobarbitone, halothane and enflurane, reversibly potentiated the function of homomeric α1 glycine receptors at concentrations which represent approximately twice the EC 50 for production of anaesthesia in mammals, but ketamine and etomidate were ineffective. 5 Two novel cyclobutane compounds were tested; the anaesthetic compound (1‐chloro‐1,2,2‐trifluorocyclobutane) from 0.5 to 5 mM potentiated the action of glycine in a concentration‐dependent manner; however, the non‐anaesthetic analogue (1,2‐dichloro‐hexfluorocyclobutane) had no effect on glycine receptor function at concentrations (25 to 80 μ m ) predicted to be anaesthetic, based on the lipid solubility of this compound. 6 These 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. Potentiation of glycine receptor function may contribute to the anaesthetic action of n‐alcohols and volatile agents.