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Inhibition of [ 3 H]‐(+)‐MK 801 binding to rat brain sections by CPP and 7‐chlorokynurenic acid: an autoradiographic analysis
Author(s) -
Tacconi S.,
Ratti E.,
Marien M.R.,
Gaviraghi G.,
Bowery N.G.
Publication year - 1993
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1111/j.1476-5381.1993.tb12845.x
Subject(s) - nmda receptor , cerebellum , binding site , glycine , chemistry , glutamate receptor , kynurenic acid , receptor , inhibitory postsynaptic potential , biochemistry , biophysics , amino acid , biology , endocrinology
1 The regional binding of [ 3 H]‐(+)‐5‐methyl‐10,11‐dihydro‐5 H ‐dibenzo( a,d )cyclohepten‐5,10‐imine maleate ([ 3 H]‐(+)‐MK 801) to sections of rat brain was measured by an in vitro quantitative autoradiographic technique. A heterogeneous distribution of binding sites was observed. 2 High values of binding were detected in the hippocampal formation and cerebral cortex, while very low binding was found in cerebellum. [ 3 H]‐(+)‐MK 801 binding was not detectable in white matter tracts or in the brain stem. 3 [ 3 H]‐(+)‐MK 801 binding was inhibited by increasing concentrations of both 7‐chlorokynurenate (1–1000 μ m ) and ((+)‐2‐carboxypiperazine‐4‐yl)propyl‐1‐phosphonic acid (CPP) (0.1–100 μ m ). High concentrations of both drugs were able to inhibit completely specific [ 3 H]‐(+)‐MK 801 binding. 4 IC 50 values calculated for both 7‐chlorokynurenate and CPP‐induced [ 3 H]‐(+)‐MK 801 binding inhibition were similar in all brain regions analyzed. 5 The inhibitory action of 7‐chlorokynurenate and that of CPP on [ 3 H]‐(+)‐MK 801 binding were reversed by addition of glycine and glutamate respectively. 6 It is concluded that activation of glycine and N‐methyl‐ d ‐aspartate (NMDA) receptors is obligatory for the binding of [ 3 H]‐(+)‐MK 801 to occur in all of the brain regions examined in the present study. Furthermore, on the basis of the similar regional sensitivities of [ 3 H]‐(+)‐MK 801 binding to the inhibitory action of 7‐chlorokynurenate and CPP, a single pharmacological classification of the NMDA receptor complex in brain is suggested. The cerebellum was not included in the study due to the very low level of [ 3 H]‐(+)‐MK 801 binding detected under the experimental conditions used.