ISSN:
1573-6903
Keywords:
Chronic benzodiazepines
;
GABA subsensitivity
;
GABA receptor subunits
;
regional heterogeneity
;
phosphorylation
Source:
Springer Online Journal Archives 1860-2000
Topics:
Medicine
Notes:
Abstract Molecular biological approaches to the GABAa receptor have resulted in new insights into the structure and pharmacology of this complex. It is known that the GABAa complex is a heterooligomer composed of multiple subunits which contain binding sites for the GABA, benzodiazepines and barbiturates. These subunits also contain regulatory sites for phosphorylation by intracellular kinases. There appear to be regional differences in the expression of the various subunits for the GABAa receptor complex. The functional significance of molecular heterogeneity is not yet known but it is expected that regional differences may result in pharmacologically diverse responses. Studies on the effects of chronic administration of diazepam have clearly delineated such regional differences. Chronic benzodiazepine administration results in the development of subsensitivity to the electrophysiological actions of GABA in the dorsal raphe, but not in GABA receptive neurons of the substantia nigra pars reticulata. Such data is consistent with regional heterogeneity in response to chronic benzodiazepine, exposure. It is hoped that by understanding GABAa receptor heterogeneity, and its molecular basis, we can improve the, existing receptor subtype specificity and pharmacology of the benzodiazepines.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1007/BF00972200
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