title: Inhibition of [3H]-(+)-MK 801 binding to rat brain sections by CPP and 7-chlorokynurenic acid: an autoradiographic analysis.
abstract: 1. The regional binding of [3H]-(+)-5-methyl-10,11-dihydro-5H-dibenzo (a,d)cyclohepten-5,10-imine maleate ([3H]-(+)-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. [3H]-(+)-MK 801 binding was not detectable in white matter tracts or in the brain stem. 3. [3H]-(+)-MK 801 binding was inhibited by increasing concentrations of both 7-chlorokynurenate (1-1000 microM) and ((+)-2-carboxypiperazine-4-yl)propyl-1-phosphonic acid (CPP) (0.1-100 microM). High concentrations of both drugs were able to inhibit completely specific [3H]-(+)-MK 801 binding. 4. IC50 values calculated for both 7-chlorokynurenate and CPP-induced [3H]-(+)-MK 801 binding inhibition were similar in all brain regions analyzed. 5. The inhibitory action of 7-chlorokynurenate and that of CPP on [3H]-(+)-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 [3H]-(+)-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 [3H]-(+)-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 [3H]-(+)-MK 801 binding detected under the experimental conditions used.
authors.affiliation: Glaxo Research Laboratories, Verona, Italy.
authors.forename: S
authors.initials: S
authors.lastname: Tacconi
authors.forename: E
authors.initials: E
authors.lastname: Ratti
authors.forename: M R
authors.initials: MR
authors.lastname: Marien
authors.forename: G
authors.initials: G
authors.lastname: Gaviraghi
authors.forename: N G
authors.initials: NG
authors.lastname: Bowery
mesh_terms: D000818:Animals; D001345:Autoradiography; D001921:Brain / Q000033:anatomy & histology / Q000187:drug effects / Q000378:metabolism*; D002531:Cerebellum / Q000187:drug effects / Q000378:metabolism; D016291:Dizocilpine Maleate / Q000378:metabolism*; D005971:Glutamates / Q000494:pharmacology; D018698:Glutamic Acid; D005998:Glycine / Q000494:pharmacology; D007091:Image Processing, Computer-Assisted; D066298:In Vitro Techniques; D007736:Kynurenic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology; D008297:Male; D010879:Piperazines / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors* / Q000187:drug effects / Q000378:metabolism
chemical_list: D005971:Glutamates; D010879:Piperazines; D016194:Receptors, N-Methyl-D-Aspartate; D018698:Glutamic Acid; D016291:Dizocilpine Maleate; C050592:3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid; D007736:Kynurenic Acid; C057013:7-chlorokynurenic acid; D005998:Glycine