Multiple benzodiazepine receptor localization by light microscopic radiohistochemistry.
Benzodiazepine receptor binding studies have been reported suggesting the existence of at least two different benzodiazepine receptors. One distinguishing feature of these two sites is that one has a high affinity for triazolopyridazines, whereas the other has a low affinity. In this study, the regional localization of the two different receptors was examined by light microscopic radiohistochemical methods. [3H]Flunitrazepam was used to label all types of benzodiazepine receptors in slide-mounted tissue sections. CL218,872, a typical triazolopyridazine, was used to preferentially displace [3H]flunitrazepam from the subclass of receptors having a high affinity for CL218,872. Autoradiographs clearly showed that receptor binding in some regions was substantially affected by CL218,872 while that in other regions was affected to a lesser degree. Areas with receptors with high affinity for the triazolopyridazine (Type 1 receptors) included the cerebellum, globus pallidus and parts of the cerebral cortex. Areas with receptors having low affinity for the drugs (Type 2 receptors) included the superficial layer of the superior colliculus, the caudate-putamen and parts of the dentate gyrus. The results of this study may help explain the physiological differences between the benzodiazepine and triazolopyridazine drugs and should point out target sites in the brain for additional studies of the apparently two different receptors.
D000818:Animals; D001345:Autoradiography; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D002531:Cerebellum / Q000378:metabolism; D005445:Flunitrazepam / Q000378:metabolism; D008636:Mesencephalon / Q000378:metabolism; D011724:Pyridazines / Q000378:metabolism; D051381:Rats; D011955:Receptors, Drug / Q000378:metabolism*; D011963:Receptors, GABA-A; D013329:Structure-Activity Relationship
D011724:Pyridazines; D011955:Receptors, Drug; D011963:Receptors, GABA-A; D005445:Flunitrazepam; C021604:CL 218872