Regionally Distinct N-Methyl-D-Aspartate Receptors Distinguished by Quantitative Autoradiography of [3H]MK-801 Binding in Rat Brain |
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Authors: | Sharin Y. Sakurai John B. Penney Anne B. Young |
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Affiliation: | Department of Neurology, University of Michigan, Ann Arbor, Michigan;Department of Neurology, Massachusetts General Hospital, Boston, Massachusetts, U.S.A. |
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Abstract: | Abstract: Quantitative autoradiography of [3H]MK-801 binding was used to characterize regional differences in N -methyl- d -aspartate (NMDA) receptor pharmacology in rat CNS. Regionally distinct populations of NMDA receptors were distinguished on the basis of regulation of [3H]MK-801 binding by the NMDA antagonist 3-(2-carboxypiperazin-4-yl)-propyl-1-phosphonic acid (CPP). CPP inhibited [3H]MK-801 binding in outer cortex (OC) and medial cortex (MC) with apparent K i values of 0.32-0.48 μ M , whereas in the medial striatum (MS), lateral striatum (LS), CA1, and dentate gyrus (DG) of hippocampus, apparent K i values were 1.1-1.6 μ M . In medial thalamus (MT) and lateral thalamus (LT) the apparent K i values were 0.78 μ M . In the presence of added glutamate (3 μ M ), the relative differences in apparent K i values between regions maintained a similar relationship with the exception of the OC. Inhibition of [3H]MK-801 binding by the glycine site antagonist 7-chlorokynurenic acid (7-ClKyn) distinguished at least two populations of NMDA receptors that differed from populations defined by CPP displacement. 7-ClKyn inhibited [3H]MK-801 binding in OC, MC, MS, and LS with apparent K i values of 6.3-8.6 μ M , whereas in CA1, DG, LT, and MT, K i values were 11.4-13.6 μ M . In the presence of added glycine (1 μ M ), the relative differences in apparent K i values were maintained. Under conditions of differential receptor activation, regional differences in NMDA receptor pharmacology can be detected using [3H]MK-801 binding. |
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Keywords: | 3-(2-Carboxypiperazin-4-yl)-propyl-1-phosphonic acid Glutamate 7-Chlorokynurenic acid MK-801 Phencyclidine N-Methyl-D-aspartate receptor |
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