Regional heterogeneity of benzodiazepine receptors at 37 degrees C: an in vitro study in various regions of the rat brain.
The most compelling pharmacological evidence in support of benzo-diazepine (BZD) receptor heterogeneity is derived from the study of the complex interactions of CL 218872 and propyl beta-carboline-3-carboxylate (PCC) with brain BZD receptors. In the present study, we provide evidence to support the hypothesis that intraregional BZD receptor heterogeneity in rat brain is a result of the different conformational states of a single receptor. This hypothesis is based upon the observation that CL 218872 and PCC lose the ability to effectively discriminate BZD receptor subtypes in rat cerebral cortex, hippocampus and pons-medulla at physiological temperature (37 degrees C). Interestingly, both PCC and CL 218872 show higher affinity for BZD receptors in the cerebellum when compared to other brain regions at 37 degrees C. This observation suggests that interregional BZD receptor heterogeneity occurs under physiologically relevant temperatures. We propose that distinct cerebellar and non-cerebellar type BZD receptors exist in vivo while marked differences in the affinity of the type I and type II BZD receptor subtypes postulated by Klepner et al. 1979 may only occur in vitro at 0 degree--4 degree C.
D000818:Animals; D001667:Binding, Competitive; D001921:Brain / Q000378:metabolism*; D002243:Carbolines / Q000378:metabolism; D002531:Cerebellum / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism; D005445:Flunitrazepam / Q000378:metabolism; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D011149:Pons / Q000378:metabolism; D011724:Pyridazines / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011956:Receptors, Cell Surface / Q000378:metabolism*; D011963:Receptors, GABA-A; D013696:Temperature
D002243:Carbolines; D011724:Pyridazines; D011956:Receptors, Cell Surface; D011963:Receptors, GABA-A; D005445:Flunitrazepam; C021604:CL 218872; C028585:propyl beta-carboline-3-carboxylate