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J Neurochem. 1993 Apr;60(4):1344-53.

Regionally distinct N-methyl-D-aspartate receptors distinguished by quantitative autoradiography of [3H]MK-801 binding in rat brain.

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1
Department of Neurology, University of Michigan, Ann Arbor.

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 Ki values of 0.32-0.48 microM, whereas in the medial striatum (MS), lateral striatum (LS), CA1, and dentate gyrus (DG) of hippocampus, apparent Ki values were 1.1-1.6 microM. In medial thalamus (MT) and lateral thalamus (LT) the apparent Ki values were 0.78 microM. In the presence of added glutamate (3 microM), the relative differences in apparent Ki 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 Ki values of 6.3-8.6 microM, whereas in CA1, DG, LT, and MT, Ki values were 11.4-13.6 microM. In the presence of added glycine (1 microM), the relative differences in apparent Ki values were maintained. Under conditions of differential receptor activation, regional differences in NMDA receptor pharmacology can be detected using [3H]MK-801 binding.

PMID:
8095974
[Indexed for MEDLINE]
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