Modulation of the Benzodiazepine-GABA Receptor Chloride Ionophore Complex by Multiple Allosteric Sites: Evidence for a Barbiturate “Receptor”
The discovery of specific recognition sites (receptors) for benzodiazepines in the central nervous system has resulted in a better understanding of the molecular pharmacology of benzodiazepines, barbiturates, and related compounds. Within the past 5 years it has become apparent that the benzodiazepine receptor is one component of a “supramolecular complex” consisting of multiple allosteric recognition sites which play a critical role in the regulation of transmembrane potential. Both neurochemical and electrophysiological studies support the notion that occupation of either the benzodiazepine-GABA receptor complex or distinct, allosteric sites for compounds such as barbiturates and cage convulsants (which are probably located on or near the chloride ionophore) can regulate the properties of this chloride channel. This chapter will review neurochemical evidence that demonstrates a functional coupling of the recognition components of the benzo-diazepine-GABA receptor chloride ionophore complex (supramolecular complex) and summarize recent findings from our laboratory demonstrating that the “effector” component of this complex, the chloride ionophore, is rapidly altered by stress.
KeywordsCage Pyridine Diazepam Halide Pentobarbital
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