Pre- versus postsynaptic localization of benzodiazepine and beta-carboline binding sites.
[3H]Flunitrazepam (FNP) and [3H]methyl beta-carboline-3-carboxylate (MCC) binding was examined in soluble and particulate fractions from membranes solubilized with Triton X-100 or in subfractions of synaptosomal membranes obtained by a physical separation technique. Results using both methods demonstrate that benzodiazepine and beta-carboline sites reside on both pre- and postsynaptic membranes. Further, subfractionation experiments indicate that the binding sites for both ligands are unequally distributed within the synapse and among brain regions. For example, in cerebral cortical presynaptic membranes there are twice as many FNP as MCC sites whereas in postsynaptic membranes this ratio is reversed. The number of FNP and MCC sites are equal in the presynaptic fraction from cerebellum. The postsynaptic membranes derived from cerebellum have three times the number of FNP compared to MCC sites. In hippocampus this ratio varies between 1.5 and 2.8 in each subfraction. These results support the idea that benzodiazepine and beta-carboline binding sites represent different recognition sites.
Tietz
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Chiu
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Rosenberg
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D000818:Animals; D002243:Carbolines / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D005445:Flunitrazepam; D006624:Hippocampus / Q000378:metabolism; D007211:Indoles / Q000378:metabolism*; D008297:Male; D011092:Polyethylene Glycols; D051381:Rats; D011963:Receptors, GABA-A / Q000378:metabolism*; D012995:Solubility; D013570:Synaptic Membranes / Q000378:metabolism*
D002243:Carbolines; D007211:Indoles; D011963:Receptors, GABA-A; D011092:Polyethylene Glycols; D005445:Flunitrazepam; C024915:beta-carboline-3-carboxylic acid ethyl ester