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Heterogeneity of γ‐Aminobutyric Acid/Benzodiazepine/β‐Carboline Receptor Complex in Rat Spinal Cord
Author(s) -
Santi M. R.,
Cox D. H.,
Guidotti A.
Publication year - 1988
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.1988.tb10576.x
Subject(s) - flumazenil , spinal cord , cerebellum , muscimol , chemistry , gabaa receptor , flunitrazepam , benzodiazepine , lateral vestibular nucleus , binding site , central nervous system , medicine , endocrinology , receptor , biochemistry , biology , neuroscience , vestibular nuclei
The properties of muscimol, β‐carboline (BC), and benzodiazepine (BZD) binding to crude synaptic membranes were studied in the spinal cord and cerebellum of rats. In cerebellar membranes, the density of high‐affinity [ 3 H]muscimol and [ 3 H]6,7‐dimethoxy‐4‐ethyl‐β‐carboline ([ 3 H]BCCM) binding sites is almost identical to that of [ 3 H]flunitrazepam ([ 3 H]FLU) or[ 3 H]flumazenil (Ro 15–1788; ethyl‐8‐fluoro‐5,6‐dihydro‐5‐methyl‐6‐oxo‐4 H ‐imidazo[1,5–α][1–4]benzodiazepine‐3‐carboxylate). In contrast to the cerebellum, the number of muscimol and BC binding sites in rat spinal cord is ∼20–25% of the number of FLU or flumazenil binding sites. Moreover, in spinal cord membranes, BC recognition site ligands displace [ 3 H]‐flumazenil bound to those sites, with low affinity and a Hill slope significantly <1; the potency of the different BCs in displacing [ 3 H]flumazenil is 25–50‐fold lower in the spinal cord than in the cerebellum. [ 3 H]Flumazenil is not displaced from spinal cord membranes by the peripheral BZD ligand Ro 5–4864 (4′‐chlorodiazepam), whereas it is displaced with low affinity and a Hill slope of < 1 (n H = 0.4) by CL 218,872 (3‐methyl‐6–(3‐trifluoromethylphenyl)‐1,2,4‐triazolol[4,3‐ b ]pyridazine). These data suggest that a large number of BZD binding sites in spinal cord (∼80%) are of the central‐type, BZD 2 subclass, whereas the BZD binding sites in cerebellum are predominately of the central‐type. BZD 1 subclass. In both cerebellar and spinal cord membranes, micromolar γ‐aminobutyric acid (GABA) enhanced the binding of [ 3 H]FLU; however, this effect is less efficacious and less potent in the spinal cord, observations indicating two possibilities: (a) that in spinal cord some of the BZD 2 binding sites are not coupled to the GABA A binding sites, or (b) that they are coupled in a GABA A /BZD 2 receptor complex containing a large proportion of BZD 2 binding sites associated with a relatively small number of GABA A binding sites.