High correlation between the localization of [3H]TCP binding and NMDA receptors
1986; Elsevier BV; Volume: 123; Issue: 1 Linguagem: Inglês
10.1016/0014-2999(86)90703-x
ISSN1879-0712
AutoresWilliam F. Magaros, Dorothy C.M. Chu, J. Timothy Greenamyre, John B. Penney, Anne B. Young,
Tópico(s)Epilepsy research and treatment
ResumoTritiated N-(1-[2-thienylcyclohexyl)-3,4-piperidine ([3H]TCP), a derivative of the dissociative anesthetic phencyclidine (PCP), has recently been shown to bind specifically to a o-opiate receptor within the central nervous system of the rat (Sircar and Zukin, 1985). Drugs of this class noncompetitively inhibit the excitatory properties of Nmethyl-D-aspartate (NMDA), a glutamate analogue, in the spinal cord (Martin and Lodge, 1985), and inhibit long-term potentiation in the hippocampus (Stringer et al., 1983). Both of these effects are thought to be mediated by NMDA-sensitive glutamate receptors. The NMDA receptor is coupled to a voltage-sensitive cation channel that is gated by Mg 2÷. It is at this.channel site that PCP and related compounds are believed to act. In order to further delineate the relationship between the dissociative anesthetics and NMDA receptors, we have compared the regional binding distribution of the o-specific compound [3H]TCP and NMDA-sensitive [3H]glutamate binding sites within the rat CNS using quantitative autoradiography. Radiolabelling of each receptor class was carried out on alternate 20 /~m thick slide mounted sections taken at various levels of rat forebrain. For [3H]TCP binding, sections were preincubated for 30 min in cold 50 mM Tris-acetate, pH 7.4 and then dried. Sections were then incubated for 45 min in the same buffer with 1 mM magnesium acetate and 20 nM [3H]TCP (52.9 Ci/mmol, New England Nuclear Corp.) in the presence or ab
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