Molecular heterogeneity of benzodiazepine receptors

Abstract

Benzodiazepines exhibit reversible, stereospecific high affinity binding to mammalian brain membranes, and the respective binding sites for ³H-flunitrazepam represent pharmacologically and clinically relevant receptors for benzodiazepines^1–3. Recently it has been demonstrated that reversibly bound ³H-flunitrazepam becomes irreversibly attached to a specific membrane protein with apparent molecular weight of 50,000 when incubations were performed in the presence of UV light^4,5. Irreversible binding of ³H-flunitrazepam to this protein had pharmacological properties similar to reversible benzodiazepine receptor binding, indicating that ³H-flunitrazepam is a photoaffinity label for the benzodiazepine receptor⁵. Using irreversible binding of ³H-flunitrazepam and subsequent electrophoretic separation of the labelled proteins in SDS-gels followed by fluorography⁶, we found that in hippocampus and several other brain regions at least two different types of benzodiazepine receptors exist. Each seems to be associated with a γ-aminobutyric acid (GABA) receptor.