Abstract:
:Brain GABAA/benzodiazepine receptors are highly heterogeneous. This heterogeneity is largely derived from the existence of many pentameric combinations of at least 16 different subunits that are differentially expressed in various brain regions and cell types. This molecular heterogeneity leads to binding differences for various ligands, such as GABA agonists and antagonists, benzodiazepine agonists, antagonists, and inverse agonists, steroids, barbiturates, ethanol, and Cl- channel blockers. Different subunit composition also leads to heterogeneity in the properties of the Cl- channel (such as conductance and open time); the allosteric interactions among subunits; and signal transduction efficacy between ligand binding and Cl- channel opening. The study of recombinant receptors expressed in heterologous systems has been very useful for understanding the functional roles of the different GABAA receptor subunits and the relationships between subunit composition, ligand binding, and Cl- channel properties. Nevertheless, little is known about the complete subunit composition of the native GABAA receptors expressed in various brain regions and cell types. Several laboratories, including ours, are using subunit-specific antibodies for dissecting the heterogeneity and subunit composition of native (no reconstituted) brain GABAA receptors and for revealing the cellular and subcellular distribution of these subunits in the nervous system. These studies are also aimed at understanding the ligand-binding, transduction mechanisms, and channel properties of the various brain GABAA receptors in relation to synaptic mechanisms and brain function. These studies could be relevant for the discovery and design of new drugs that are selective for some GABAA receptors and that have fewer side effects.
journal_name
Mol Neurobioljournal_title
Molecular neurobiologyauthors
De Blas ALdoi
10.1007/BF02740747subject
Has Abstractpub_date
1996-02-01 00:00:00pages
55-71issue
1eissn
0893-7648issn
1559-1182journal_volume
12pub_type
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