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Differential action of NMDA antagonists on cholinergic neurotoxicity produced by N-methyl-D-aspartate and quinolinic acid
| Content Provider | Scilit |
|---|---|
| Author | Pawley, A. C. Flesher, S. Boegman, R. J. Beninger, R. J. Jhamandas, K. H. |
| Copyright Year | 1996 |
| Description | Journal: British Journal of Pharmacology 1. Injections of N-methyl-D-aspartate (NMDA) and quinolinic acid (Quin), agonists that activate NMDA receptors, into the rat nucleus basalis magnocellularis (nbM) produced a dose-related decrease in cholineacetyltransferase (ChAT) activity in the cerebral cortex and amygdala 7 days after injection. 2. In order to examine the possibility that NMDA and Quin activate different sub-types of NMDA receptors to produce central cholinergic neurotoxicity, the sensitivity of these agonists to the action of three different NMDA receptor antagonists, 2-amino-7-phosphonoheptanoate (AP-7), 7-chlorokynurenate and dizolcipine (MK801) was examined by injecting a fixed dose of NMDA (60 nmol) or Quin (120 nmol) in combination with different doses of the antagonists into the nbM. 3. Both AP-7 (0.6-15 nmol) and 7-chlorokynurenate (3.75-200 nmol), which block the NMDA receptor recognition site and glycine modulatory site respectively, produced a dose-related attenuation of the NMDA or Quin-induced decrease in ChAT activity in both the cortex and amygdala. Both antagonists showed a greater potency against the action of NMDA than against Quin. 4. MK801 (2-200 nmol), an NMDA receptor-linked channel blocker, attenuated the Quin and NMDA response only at a high dose. Unlike AP-7 and 7-chlorokynurenate, MK801 did not exhibit a consistent difference in its potency as an antagonist against NMDA and Quin. 5. The differential antagonist actions of AP-7 or 7-chlorokynurenate against NMDA and Quin-induced cholinergic neurotoxicity suggest that the excitotoxic actions of these two agonists are mediated via distinct NMDA receptor sub-types. The NMDA- and Quin-sensitive receptors appear to differ with respect to properties of the receptor recognition and glycine modulatory sites that are associated with these receptors. |
| Related Links | http://europepmc.org/articles/pmc1909798?pdf=render http://onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.1996.tb16697.x/pdf |
| Ending Page | 1064 |
| Page Count | 6 |
| Starting Page | 1059 |
| e-ISSN | 14765381 |
| DOI | 10.1111/j.1476-5381.1996.tb16697.x |
| Journal | British Journal of Pharmacology |
| Issue Number | 6 |
| Volume Number | 117 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 1996-03-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: British Journal of Pharmacology N‐methyl‐d‐aspartate (nmda) Quinolinic Acid (quin) Nmda Receptor Antagonists |
| Content Type | Text |
| Resource Type | Article |
