ISSN:
1471-4159
Source:
Blackwell Publishing Journal Backfiles 1879-2005
Topics:
Medicine
Notes:
Abstract: 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 [3H]muscimol and [3H]6,7-dimethoxy-4-ethyl-β-carboline ([3H]BCCM) binding sites is almost identical to that of [3H]flunitrazepam ([3H]FLU) or[3H]flumazenil (Ro 15–1788; ethyl-8-fluoro-5,6-dihydro-5-methyl-6-oxo-4H-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 [3H]-flumazenil bound to those sites, with low affinity and a Hill slope significantly 〈1; the potency of the different BCs in displacing [3H]flumazenil is 25–50-fold lower in the spinal cord than in the cerebellum. [3H]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 (nH= 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, BZD2 subclass, whereas the BZD binding sites in cerebellum are predominately of the central-type. BZD1 subclass. In both cerebellar and spinal cord membranes, micromolar γ-aminobutyric acid (GABA) enhanced the binding of [3H]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 BZD2 binding sites are not coupled to the GABAA binding sites, or (b) that they are coupled in a GABAA/BZD2 receptor complex containing a large proportion of BZD2 binding sites associated with a relatively small number of GABAA binding sites.
Type of Medium:
Electronic Resource
URL:
http://dx.doi.org/10.1111/j.1471-4159.1988.tb10576.x
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