Benutzerhandbuch Datenschutzhinweis Impressum Kontakt





Molecular biology of the GABAA receptor


Seeburg,  Peter H.
Department of Molecular Neurobiology, Max Planck Institute for Medical Research, Max Planck Society;

Volltexte (frei zugänglich)
Es sind keine frei zugänglichen Volltexte verfügbar
Ergänzendes Material (frei zugänglich)
Es sind keine frei zugänglichen Ergänzenden Materialien verfügbar

Barnard, E. A., Darlison, M. G., Fujita, N., Glencorse, T. A., Levitan, E. S., Reale, V., et al. (1988). Molecular biology of the GABAA receptor. Advances in Experimental Medicine and Biology, 236, 31-45. doi:10.1007/978-1-4757-5971-6_3.

The GABAA receptorreceptor is the major molecular site of the ubiquitous inhibitory acEivities of the brain, being present on the great majority of mammalian brain neurones (1). Electrophysiological studies and, especially, recent patch-clamp studies on cultured neurones (2,3) have established that at these sites GABA opens a chloride channel which is integrally associated with its receptor. Further, the GABAA receptor at brain synapses is known to be a site of action of several pharmacologically important classes of drugs. Pharmacological and ligand-binding studies (reviewed in Ref. 4) have identified at least 5 types of binding site on this receptor: (i) the GABA agonist/antagonist site; (ii) the benzodiazepine site, which itself is complex, having interactions with both anxiolytic agonists and anxiogenic “inverse agonists” (5); (iii) the picrotoxin site, where agents such as picrotoxin (5) or t-butylbicyclophosphorothionate (6) block the GABA-activated channel; (iv) the depressant site, recognising the CNS-depressant barbiturates and certain other depressant drugs which prolong the lifetime of the GABA-activated channel (3); this site, also, appears to be multiple, since certain steroids (7), the anaesthetic propanadid (8) and avermectin Bla (9,10) act similarly to depressants in some but not all ways; (v) sites binding the channel-permeating anions (but not other ions) (2,4). Each of these types of ligand site can interact allosterically with one or more of the other types (4). From this network of interactions, it can be deduced that several of these sites can be occupied by their respective ligands simultaneously and that each of the 5 or more types of site must be physically separate on the receptor structure.