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Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)

Enhancement of gamma-aminobutyric acidA receptor activity by alpha-chloralose.

alpha-Chloralose is widely used as an anesthetic in the laboratory due to its minimal effects on autonomic and cardiovascular systems, yet little is known about its mechanism of action. We examined the effects of alpha-chloralose on gamma-aminobutyric acid type A (GABAA) receptor activity because recent studies have shown that several classes of general anesthetics modulate the function of this receptor. GABAA receptor activity was assayed by measuring the GABA-induced current in Xenopus oocytes expressed with human GABAA receptor alpha-1, beta-1 and gamma-2L subunits. alpha-Chloralose produced a concentration-dependent potentiation of the GABA-induced current with an EC50 value of 49 microM and a maximal effect of 239% of control. Membrane current was not affected by alpha-chloralose in the absence of GABA. alpha-Chloralose (100 microM) increased the affinity for GABA 5-fold and produced a small (17%) increase in the efficacy of GABA. Measurement of the reversal potentials for the alpha-chloralose response suggested that the effect is mediated through increased Cl- conductance. Studies of alpha-chloralose interactions with other allosteric modulators determined that alpha-chloralose binds to a site on the GABAA receptor complex distinct from the benzodiazepine, neurosteroid and barbiturate sites. Chloral hydrate, trichloroethanol and urethane also augmented GABA-induced currents. alpha-Chloralose had no effect on the hydroxytryptamine-induced currents in oocytes expressed with the 5-hydroxytryptamine3 receptor. These data extend the number of classes of anesthetics that allosterically modulate GABAA receptor activity and indicate that GABAA receptors may be a common site of action for diverse classes of general anesthetics.[1]


  1. Enhancement of gamma-aminobutyric acidA receptor activity by alpha-chloralose. Garrett, K.M., Gan, J. J. Pharmacol. Exp. Ther. (1998) [Pubmed]
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