Specific Binding of [3H] phencyclidine in rat central nervous tissue: further characterization and technical considerations

摘要: Abstract The interaction of phencyclidine (PCP) with its specific receptor sites in the central nervous system has been further characterized. Kinetic association and dissociation rate constants 2.9 × 106 M−1 4.8 10−1 were determined, yielding a kinetic KD 1.6 10−7 M, agreement previously determined at equilibrium. Permissible separation time 13 s was calculated from data, well above actual less than 10 rapid filtration assay. Presoaking filters 0.01% poly- l -lysine eliminated displacable [3H]PCP adsorption to filter material. Binding data obtained via centrifigation assays identical that method. Stereospecificity PCP demonstrated by finding (+)-ketamine is four-fold more potent (−)-ketamine displacing specifically bound [3H]PCP. Several proteolytic enzymes including trypsin, papain thermolysin potently inactivated receptors. Detailed regional distribution studies showed highest density receptors subicular cortex hippocampus, intermediate levels hypothalamus, striatum, frontal cerebellum, lower brainstem spinal cord, negligible corpus callosum, white- matter control area. Benzomorphan opiates PCP-like behavioral effects interact receptor. These support pharmacological relevance site as