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Localization of N-Methyl-d-Aspartate Receptors in the Rat Striatum: Effects of Specific Lesions on the [3H]3-(2-Carboxypiperazin-4-yl)propyl-1-Phosphonic Acid Binding
| Content Provider | Scilit |
|---|---|
| Author | Samuel, Denise Errami, Mohammed Nieoullon, André |
| Copyright Year | 1990 |
| Description | Journal: Journal of Neurochemistry The binding of [3H]3-(2-carboxypiperazin-4-yl)propyl-1-phosphonic acid ([3H]CPP), a rigid analogue of 2-amino-7-phosphonoheptanoic acid (AP7) and reported to be a selective N-methyl-D-aspartate (NMDA) antagonist, was studied in rat striatal membranes using a centrifugation procedure to separate bound and free radioligand. [3H]CPP bound with high affinity (KD = 272 nM) in a saturable, reversible, and protein concentration-dependent manner. Specific binding was suggested to involve a single class of noninteracting binding sites. The most potent [3H]CPP binding inhibitors tested were CPP, L-glutamate, 2-amino-5-phosphonovalerate, and AP7. NMDA, L-aspartate, and alpha-aminoadipate were also shown to be efficient in inhibiting the binding, whereas quisqualate, D,L-2-amino-4-phosphonobutyrate, kainate, L-glutamate diethylester, and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid were found to be essentially inactive. These data are therefore consistent with the view that [3H]CPP selectively binds to NMDA receptors in the rat striatum. Lesions of intrastriatal neurons using local injections of kainic acid revealed a marked decrease in [3H]CPP binding, suggesting an almost exclusively postsynaptic location of binding sites in the striatum. Conversely, bilateral lesion of corticostriatal glutamatergic fibers resulted in an increased number of [3H]CPP striatal binding sites, providing evidence for a putative supersensitivity response to this striatal deafferentation. Interestingly, lesion of the nigrostriatal dopaminergic neurons using intranigral 6-hydroxydopamine injections resulted, 2-3 weeks later, in a similar increase in the number of [3H]CPP striatal binding sites.(ABSTRACT TRUNCATED AT 250 WORDS) |
| Related Links | http://onlinelibrary.wiley.com/doi/10.1111/j.1471-4159.1990.tb04893.x/pdf |
| Ending Page | 1933 |
| Page Count | 8 |
| Starting Page | 1926 |
| e-ISSN | 14714159 |
| DOI | 10.1111/j.1471-4159.1990.tb04893.x |
| Journal | Journal of Neurochemistry |
| Issue Number | 6 |
| Volume Number | 54 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 1990-06-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: Journal of Neurochemistry Glutamate Receptors 3‐(2‐carboxypiperazin‐4‐yl)propyl‐1‐phosphonic Acid Nigrostriatal Dopaminergic System |
| Content Type | Text |
| Resource Type | Article |
