GABAa receptors expression

BoEeau AJ, Baur R, Sharkey LM, Sigel E, Czajkowski C. 2002. The relative amount of cRNA coding for y2 subunits affects stimulation by benzodiazepines in GABAa receptors expressed in Xenopus oocytes. Neuropharmacology 43 695. 

Woodward RM, Polenzani L, Miledi R. 1994. Effects of fena-mates and other nonsteroidal anti-inflammatory drugs on rat brain GABAA receptors expressed in Xenopus oocytes. J Pharmacol Exp Ther 268 (2) 806. 

Bouilleret V, Loup F, Kiener T, Marescaux C, Fritschy JM (2000) Early loss of internemons and delayed subunit-specific changes in GABAA-receptor expression in a mouse model of mesial temporal lobe epilepsy. Hippocampus 10 305-324... 

Aoshima, H. and Hamamoto, K. 1999. Potentiation of GABAA receptors expressed in Xenopus oocytes by perfume and phytoncid. 63(4) 743-748. 

Mice lacking the 8 subunit, which is mainly expressed in cerebellum and thalamus, display an attenuation of ssatrighting reflex time following the administration of the neurosteroids, alphaxalone and pregnanolone, while the responses to propofol, etomindate, ketamine and the benzodiazepine midazolam were unaffected. This demonstrates the role of GABAa receptors containing the 8 subunit for neurosteroid action. 

Figure 11.7 Presumed arrangement of GABAa receptor subunits to form a receptor-channel complex, (a) Diagrammatic representation of an individual subunit with four transmembrane regions, extracellular sites for glycosylation and a site for phosphorylation on the intracellular loop between M3 and M4. (b) Association of five subunits to form a central ionophore bounded by the M2 region of each subunit. The suggested stoichiometry of the most widely expressed form of receptor is 2a, 2 and ly. Shown below are the possible subunit combinations of one such benzodiazepine-sensitive receptor together with a benzodiazepine-insensitive receptor in which the 7 subunit is replaced by a c5, and a ti-containing receptor with four different subunit types...

Intracellular steroid receptors, which alter gene expression, exist for corticosteroids, oestrogens and progesterone in the brain, as in the periphery but they cannot account for the relatively rapid depression of CNS function induced by some steroids. This was explained when Harrison and Simmonds (1984) discovered that alphaxalone (the steroid anaesthetic) potentiated the duration of GABA-induced currents at the GABAa receptor in slices of rat cuneate nucleus just like the barbiturates (Fig. 13.6). Of the... 

Figure 19.8 A schematic representation of the GABAa receptor shift hypothesis. This proposes that patients with panic disorder have dysfunctional GABAa receptors such that the actions of drugs that behave as antagonists in normal subjects are expressed as inverse agonism in panic patients. It is unlikely that this theory extends to generalised anxiety disorder (GAD), for which benzodiazepine agonists are highly effective treatments, but it could explain why these drugs are relatively ineffective at treating panic disorder. (Based on Nutt et al. 1990)...

Moragues, N., Ciofi, P., Lafon, P., Tramu, G., Garret, M. (2003). GABAa receptor epsilon subunit expression in identified peptidergic neurons of the rat hypothalamus. Brain Res. 967, 285-9. 

Wisden, W Herb, A., Wieland, H., Keinanen, K Liiddens, H and Seeburg, P. H. (1991) Cloning, pharmacological characteristics and expression pattern of the rat GABAA receptor alpha 4 subunit. FEBS Lett. 289,227-230. 

---