Molecular mechanisms regulating the interactions between the benzodazepines and GABA receptors in the central nervous system.
Using radioreceptor assay techniques to measure the kinetics of GABA and diazepam receptors, a relationship between GABA and benzodiazepine receptors has been firmly established in membranes of brain and neuroblastoma NB2a clonal cell lines. Occupancy of benzodiazepine receptors uncovers a new population of GABA receptors (GABA2 receptors) endowed with high affinity for GABA. Moreover, stimulation of GABA receptors increases the affinity of 1,4-benzodiazepine receptors for 1,4-benzodiazepines. This reciprocal interaction appears to be mediated by an endogenous regulatory protein (for details on this protein see [14 and 29]) which allosterically regulates GABA2 receptors while it competitively interacts with benzodiazepines for their specific binding sites. The rank order of potency of the various 1,4-benzodiazepines to block the action of this protein inhibitor on GABA receptors is related to their capacity to displace 3H-diazepam binding. These data suggest that the interaction between the 1,4-benzodiazepine receptors and the endogenous protein modulator of GABA2 receptors might play a role in the pharmacological action of the 1,4-benzodiazepines.
D000818:Animals; D014151:Anti-Anxiety Agents / Q000378:metabolism*; D001569:Benzodiazepines; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D051379:Mice; D009447:Neuroblastoma / Q000378:metabolism; D011955:Receptors, Drug / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D014151:Anti-Anxiety Agents; D011955:Receptors, Drug; D001569:Benzodiazepines; D005680:gamma-Aminobutyric Acid