Topic
NS102
About: NS102 is a research topic. Over the lifetime, 10 publications have been published within this topic receiving 215 citations.
Papers
TL;DR: The results demonstrate the lack of complete selectivity amongst some available competitive antagonists for AMPA and kainate receptors, and indicate that kainates receptors expressed by hippocampal cells lack the cyclothiazide modulatory site present at AMPA receptors.
Abstract: Native kainate receptors expressed by cultured hippocampal cells were studied in the whole-cell configuration of the patch-clamp technique by using a fast perfusion system. About 80% of the neurons expressed kainate receptors independently of the time in culture (0-4 days), which coincided with the number of cells immunoreactive for a monoclonal antibody against the GluR5/6/7 subunits. Three types of cells were considered: neurons in which the rapid application of kainate induced a rapidly desensitizing current, cells in which kainate induced a more slowly rising, non-desensitizing, response and those in which a mixture of both responses was apparent. Steady responses induced by 300 microM kainate were inhibited by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) in a dose-dependent manner (IC50 = 0.92 microM). CNQX was less potent in blocking transient kainate-induced responses (IC50 = 6.1 microM). Responses to kainate, whether steady or transient, were also inhibited by NS102, showing poor selectivity for the transient response (IC50 = 4.1 and 2.2 microM respectively). The new alpha-amino-3-hydroxy-5-methyl-4-isoxazole (AMPA) receptor antagonist NS394 was very potent in inhibiting steady kainate-induced currents (IC50 = 0.45 microM), but was even more effective in preventing peak responses (IC50 = 0.13 microM). In contrast, cyclothiazide did not affect transient kainate-induced responses but did potentiate current induced by activation of AMPA receptors by AMPA or kainate. These results demonstrate the lack of complete selectivity amongst some available competitive antagonists for AMPA and kainate receptors, and indicate that kainate receptors expressed by hippocampal cells lack the cyclothiazide modulatory site present at AMPA receptors. In addition, the present data support the idea that low-affinity kainate binding sites in the brain correspond to receptor channels selectively activated by kainate.
53 citations
TL;DR: GluR6, one subunit of kainate receptor, plays a critical role in inducing JNK3 activation after ischemic injury, and administration of NS102 before cerebral ischemia significantly increased the number of the surviving hippocampal CA1 pyramidal cells at 5 days of reperfusion.
46 citations
TL;DR: Based on the antagonist profiles obtained, the four receptors here analyzed all belong to the AMPA-preferring subclass of glutamate receptors; however, they appear to differ from each other, probably due to differences in subunit composition.
31 citations
TL;DR: Data indicate that [3H]NBQX provides a useful novel tool to characterise the antagonist binding properties of AMPA receptors, and it is interesting that NBQX and CNQX displaced significantly more [3h]NBZX than any of the agonists tested.
Abstract: 6-Nitro-7-sulphamoylbenzo[f]quinoxaline-2,3-drone (NBOX) is a competitive antagonist selective for α-amino-3-hydroxy-5-methylisoxazole-4-propionate (AMPA) receptors. Here we report the pharmacological characteristics and anatomical distribution of [ 3 H]NBQX binding to rat brain. The association rate of [ 3 H]NBQX to rat cerebrocortical membranes was rapid, with peak binding occurring within 10 min at 0°C. The off-rate was also rapid, with near-complete dissociation of the radioligand within 5 min of addition of 1 mM unlabelled L-glutamate. [ 3 H]NBQX bound to a single class of sites with K D and B max values of 47 nM and 2.6 pmol mg -1 of protein, respectively. The rank order of inhibition of [ 3 H] NBQX binding by AMPA receptor ligands was NBQX >> 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX) ≥ (S)-5-fluorowillardiine ≥ AMPA >> L-glutamate. The chaotrope KSCN had no effect on the IC 50 value of unlabelled NBQX displacement of [ 3 H]NBQX binding. The kainate receptor-selective ligands NS102 and kainate were only very weak displacers. It is interesting that NBQX and CNQX displaced significantly more [ 3 H]NBQX than any of the agonists tested. Autoradiographic analysis of the binding of [ 3 H]NBQX to coronal sections showed a distribution compatible with that of [ 3 H]AMPA binding. These data indicate that [ 3 H]NBQX provides a useful novel tool to characterise the antagonist binding properties of AMPA receptors.
28 citations
TL;DR: The results strongly suggest that hypothermia decreased the increased assembly of the GluR6‐PSD95‐MLK3 signaling module and the activation of JNK pathway induced by I/R through KAR, which gave a new insight into the ischemic therapy.
Abstract: Kainate receptor containing GluR6 subunit (KAR) is involved in the neuronal cell death induced by cerebral ischemia/reperfusion (I/R). Hypothermia is an effective neuroprotectant in brain ischemia, whereas the neuroprotective mechanisms have not been clearly established. The present study was set out to examine whether hypothermia would cause the alternation of the assembly of the GluR6-PSD95-MLK3 signaling module and the activation of c-Jun N-terminal kinase (JNK) pathway through KAR. Hypothermia (32 degrees C) was induced 10 min before ischemia and was maintained for 3 h after ischemia. Our results indicated that hypothermia could inhibit the assembly of GluR6-PSD95-MLK3 signaling module and suppressed the activation of MLK3, MKK4/7, and JNK3. The inhibition of JNK3 activation by hypothermia diminished the phosphorylation of the transcription factor c-Jun and downregulated FasL expression in hippocampal CA1. Meanwhile, the inhibition of JNK3 activation by hypothermia attenuated bax translocation, the release of cytochrome c, and the activation of caspase-3 in CA1 subfields. Both GluR6 antagonist NS102 and GluR6 antisense oligodeoxynucleotides partly blocked the aforementioned effects of hypothermia, which was further confirmed by histology. Taken together, our results strongly suggest that hypothermia decreased the increased assembly of the GluR6-PSD95-MLK3 signaling module and the activation of JNK pathway induced by I/R through KAR, which gave a new insight into the ischemic therapy.
24 citations
Related Topics (5)
Performance Metrics
| Year | Papers |
|---|---|
| 2017 | 1 |
| 2013 | 1 |
| 2012 | 1 |
| 2011 | 1 |
| 2010 | 1 |
| 2008 | 1 |