Molecular heterogeneity of benzodiazepine receptors.
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. 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 are performed in the presence of UV light. 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 receptor. Using irreversible binding of 3H-flunitrazepam and subsequent electrophoretic separation of the labelled proteins in SDS-gels followed by fluorography, 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 gamma-aminobutyric acid (GABA) receptor.
D000818:Animals; D001569:Benzodiazepines / Q000378:metabolism*; D001921:Brain / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D005445:Flunitrazepam / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism; D008970:Molecular Weight; D009419:Nerve Tissue Proteins / Q000378:metabolism; D051381:Rats; D011955:Receptors, Drug / Q000378:metabolism*; D011963:Receptors, GABA-A; D017981:Receptors, Neurotransmitter / Q000378:metabolism*; D005680:gamma-Aminobutyric Acid / Q000378:metabolism*
D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D011955:Receptors, Drug; D011963:Receptors, GABA-A; D017981:Receptors, Neurotransmitter; D001569:Benzodiazepines; D005680:gamma-Aminobutyric Acid; D005445:Flunitrazepam