Photoaffinity labelling of benzodiazepine receptors: lack of effect on ligand binding to the nucleoside transport system.
This study was undertaken to investigate the possibility of an allosteric interaction between benzodiazepine receptors and the CNS nucleoside transport system. Irreversible (photoaffinity) labelling of the benzodiazepine receptors in guinea pig cortical membranes resulted in a marked reduction in the binding (Bmax) of both [3H]flunitrazepam (71%) and [3H]ethyl-beta-carboline-3-carboxylate (22%) to the benzodiazepine receptors but had no effect on the binding of [3H]nitrobenzylthioinosine to the nucleoside transport system. Furthermore, although photoaffinity labelling resulted in a significant decrease in the affinities of flunitrazepam (approximately equal to 16-fold) and dipyridamole (approximately equal to sevenfold) for the [3H]Ro 15-1788 binding site of the benzodiazepine receptor complex, the affinities of these compounds for the nucleoside transport system were unaltered. These results suggest that the CNS nucleoside transport system and the benzodiazepine receptor complex are distinct, noninteractive ligand recognition sites.
Hammond
J R
JR
D000345:Affinity Labels / Q000378:metabolism*; D000818:Animals; D001570:Benzodiazepinones / Q000378:metabolism; D001693:Biological Transport, Active; D002243:Carbolines / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D004176:Dipyridamole / Q000378:metabolism; D005442:Flumazenil; D005445:Flunitrazepam / Q000378:metabolism; D006168:Guinea Pigs; D009705:Nucleosides / Q000378:metabolism*; D010777:Photochemistry; D011963:Receptors, GABA-A / Q000378:metabolism*; D013868:Thioinosine / Q000031:analogs & derivatives / Q000378:metabolism
D000345:Affinity Labels; D001570:Benzodiazepinones; D002243:Carbolines; D009705:Nucleosides; D011963:Receptors, GABA-A; D005442:Flumazenil; D013868:Thioinosine; D005445:Flunitrazepam; D004176:Dipyridamole; C024915:beta-carboline-3-carboxylic acid ethyl ester; C001789:4-nitrobenzylthioinosine