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Selective reduction of N-methyl-D-aspartate-evoked responses by 1,3-di(2-tolyl)guanidine in mouse and rat cultured hippocampal pyramidal neurones
| Content Provider | Scilit |
|---|---|
| Author | Fletcher, Elizabeth J. Church, John Abdel-Hamid, Khaled Donald, John F. Mac |
| Copyright Year | 1993 |
| Description | Journal: British Journal of Pharmacology 1 The effects of 1,3-di(2-tolyl)guanidine (DTG) were examined on the responses of cultured hippocampal neurones to the excitatory amino acid analogues N-methyl-d-aspartate (NMDA), kainate, quisqualate and (RS)-α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA). 2 In rat hippocampal neurones loaded with the $Ca^{2+}$-sensitive dye Fura-2, DTG (10–100 μm) produced a concentration-dependent depression of the NMDA-evoked rises in intracellular free calcium ([Ca^{2+}$]_{i}$), an effect that was not modified by changes in the extracellular glycine concentration. DTG (at 50 and 100 μm) also attenuated, although to a lesser extent, the rises in [Ca^{2+}$]_{i}$ evoked by naturally-derived quisqualate. In contrast, 50 and 100 μm DTG did not depress responses evoked by kainate, AMPA and synthetic, glutamate-free (+)-quisqualate although on occasions DTG enhanced kainate-and AMPA-evoked rises in [Ca^{2+}$]_{i}$. 3 DTG attenuated NMDA-evoked currents recorded from mouse hippocampal neurones under whole-cell voltage-clamp with an $IC_{50}$ (mean ± s.e.mean) of 37 ± 5 μm at a holding potential of −60 mV. The DTG block of NMDA-evoked responses was not competitive in nature and was not dependent on the extracellular glycine or spermine concentration. The block did, however, exhibit both voltage-, and use-, dependency. The steady-state current evoked by naturally-derived quisqualate was also attenuated by DTG whereas those evoked by kainate and AMPA were not. 4 We conclude that DTG, applied at micromolar concentrations, is a selective NMDA antagonist in cultured hippocampal neurones, the block exhibiting both $Mg^{2+}$- and phencyclidine-like characteristics. Given the nanomolar affinity of DTG for σ binding sites it is unlikely that the antagonism observed here is mediated by σ-receptors, but the data emphasize the potential danger of ascribing the functional consequences of DTG administration solely to σ receptor-mediated events. |
| Related Links | http://europepmc.org/articles/pmc2175731?pdf=render https://onlinelibrary.wiley.com/doi/pdf/10.1111/j.1476-5381.1993.tb13749.x |
| Ending Page | 1205 |
| Page Count | 10 |
| Starting Page | 1196 |
| e-ISSN | 14765381 |
| DOI | 10.1111/j.1476-5381.1993.tb13749.x |
| Journal | British Journal of Pharmacology |
| Issue Number | 4 |
| Volume Number | 109 |
| Language | English |
| Publisher | Wiley-Blackwell |
| Publisher Date | 1993-08-01 |
| Access Restriction | Open |
| Subject Keyword | Journal: British Journal of Pharmacology Glutamate Receptors N-methyl-d-aspartate (nmda) (rs)-α-amino-3-hydroxy-5-methylisoxazole-4-propionate (ampa) 3-di(2-tolyl)guanidine (dtg) Cultured Hippocampal Pyramidal Neurones |
| Content Type | Text |
| Resource Type | Article |
