2006
DOI: 10.1124/jpet.106.104844
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Identification of Structures within GABAAReceptor α Subunits That Regulate the Agonist Action of Pentobarbital

Abstract: Barbiturates act on GABA A receptors (GABARs) through three distinct mechanisms, resulting in positive allosteric modulation, direct activation, and inhibition. These effects are observed at different concentrations and are differentially affected by some mutations and by the receptor's subunit composition. Mammalian GABARs can be formed from a combination of 16 different subunit subtypes. Although the effect of barbiturates depends largely on the ␤ subunit, their agonist activity is substantially influenced b… Show more

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Cited by 29 publications
(17 citation statements)
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“…In this study, pentobarbital produced a sizeable enhancement of the current elicited by 10 μM GABA, which was not different between oocytes incorporating GABA A receptors from control or epileptic specimens (Figure 3A, B). There was no significant current elicited by 100 μM pentobarbital in the absence of GABA in any specimen tested (Figure 3B), consistent with previous studies demonstrating that its direct agonist effect is primarily seen with receptors expressing the α 6 subunit (Drafts and Fisher, 2006), which are found exclusively in the cerebellum (Fritschy and Brunig, 2003). …”
Section: Resultssupporting
confidence: 90%
“…In this study, pentobarbital produced a sizeable enhancement of the current elicited by 10 μM GABA, which was not different between oocytes incorporating GABA A receptors from control or epileptic specimens (Figure 3A, B). There was no significant current elicited by 100 μM pentobarbital in the absence of GABA in any specimen tested (Figure 3B), consistent with previous studies demonstrating that its direct agonist effect is primarily seen with receptors expressing the α 6 subunit (Drafts and Fisher, 2006), which are found exclusively in the cerebellum (Fritschy and Brunig, 2003). …”
Section: Resultssupporting
confidence: 90%
“…The positive GABA A receptor modulator barbiturate pentobarbital also failed to substitute for 2000 ppm toluene vapor in the present study. A number of lines of evidence suggest that the positive allosteric modulatory effects of barbiturates are primarily (Cestari et al, 1996; Hanek et al, 2010; Pistis et al, 1999), although not exclusively (Drafts and Fisher, 2006), beta subunit dependent. Combined, these data suggest that toluene may not be acting through either the neurosteroid binding site nor through the barbiturate binding domain.…”
Section: Discussionmentioning
confidence: 99%
“…Thus, it would appear that barbiturate actions on GABA A Rs are more complex than with other anesthetics [63]. This observation is supported by the fact that thiopental is a more effective agonist than GABA in receptors containing α6 subunits [14]. …”
Section: Intravenous Anestheticsmentioning
confidence: 99%