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題名 mGluR5 positive modulators both potentiate activation and restore inhibition in NMDA receptors by PKC dependent pathway
作者 Chen, Hwei-Hsien ; Liao, Pei-Fei ; Chan, Ming-Huan
詹銘煥
貢獻者 神科所
日期 2011.02
上傳時間 9-Apr-2014 17:44:09 (UTC+8)
摘要 Background
     In order to understand the interaction between the metabotropic glutamate subtype 5 (mGluR5) and N-methyl-D-aspartate (NMDA) receptors, the influence of mGluR5 positive modulators in the inhibition of NMDA receptors by the noncompetitive antagonist ketamine, the competitive antagonist D-APV and the selective NR2B inhibitor ifenprodil was investigated.
     
     Methods
     This study used the multi-electrode dish (MED) system to observe field potentials in hippocampal slices of mice.
     
     Results
     Data showed that the mGluR5 agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG), as well as the positive allosteric modulators 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl) benzamide (CDPPB) and 3,3`-difluorobenzaldazine (DFB) alone did not alter the basal field potentials, but enhanced the amplitude of field potentials induced by NMDA. The inhibitory action of ketamine on NMDA-induced response was reversed by CHPG, DFB, and CDPPB, whereas the blockade of NMDA receptor by D-APV was restored by CHPG and CDPPB, but not by DFB. Alternatively, activation of NMDA receptors prior to the application of mGluR5 modulators, CHPG was able to enhance NMDA-induced field potentials and reverse the suppressive effect of ketamine and D-APV, but not ifenprodil. In addition, chelerythrine chloride (CTC), a protein kinase C (PKC) inhibitor, blocked the regulation of mGluR5 positive modulators in enhancing NMDA receptor activation and recovering NMDA receptor inhibition. The PKC activator (PMA) mimicked the effects of mGluR5 positive modulators on enhancing NMDA receptor activation and reversing NMDA antagonist-evoked NMDA receptor suppression.
     
     Conclusion
     Our results demonstrate that the PKC-dependent pathway may be involved in the positive modulation of mGluR5 resulting in potentiating NMDA receptor activation and reversing NMDA receptor suppression induced by NMDA antagonists.
關聯 Journal of Biomedical Science,18(1), 19
資料類型 article
DOI http://dx.doi.org/10.1186/1423-0127-18-19
dc.contributor 神科所en_US
dc.creator (作者) Chen, Hwei-Hsien ; Liao, Pei-Fei ; Chan, Ming-Huanen_US
dc.creator (作者) 詹銘煥zh_TW
dc.date (日期) 2011.02en_US
dc.date.accessioned 9-Apr-2014 17:44:09 (UTC+8)-
dc.date.available 9-Apr-2014 17:44:09 (UTC+8)-
dc.date.issued (上傳時間) 9-Apr-2014 17:44:09 (UTC+8)-
dc.identifier.uri (URI) http://nccur.lib.nccu.edu.tw/handle/140.119/65236-
dc.description.abstract (摘要) Background
     In order to understand the interaction between the metabotropic glutamate subtype 5 (mGluR5) and N-methyl-D-aspartate (NMDA) receptors, the influence of mGluR5 positive modulators in the inhibition of NMDA receptors by the noncompetitive antagonist ketamine, the competitive antagonist D-APV and the selective NR2B inhibitor ifenprodil was investigated.
     
     Methods
     This study used the multi-electrode dish (MED) system to observe field potentials in hippocampal slices of mice.
     
     Results
     Data showed that the mGluR5 agonist (RS)-2-chloro-5-hydroxyphenylglycine (CHPG), as well as the positive allosteric modulators 3-cyano-N-(1,3-diphenyl-1H-pyrazol-5-yl) benzamide (CDPPB) and 3,3`-difluorobenzaldazine (DFB) alone did not alter the basal field potentials, but enhanced the amplitude of field potentials induced by NMDA. The inhibitory action of ketamine on NMDA-induced response was reversed by CHPG, DFB, and CDPPB, whereas the blockade of NMDA receptor by D-APV was restored by CHPG and CDPPB, but not by DFB. Alternatively, activation of NMDA receptors prior to the application of mGluR5 modulators, CHPG was able to enhance NMDA-induced field potentials and reverse the suppressive effect of ketamine and D-APV, but not ifenprodil. In addition, chelerythrine chloride (CTC), a protein kinase C (PKC) inhibitor, blocked the regulation of mGluR5 positive modulators in enhancing NMDA receptor activation and recovering NMDA receptor inhibition. The PKC activator (PMA) mimicked the effects of mGluR5 positive modulators on enhancing NMDA receptor activation and reversing NMDA antagonist-evoked NMDA receptor suppression.
     
     Conclusion
     Our results demonstrate that the PKC-dependent pathway may be involved in the positive modulation of mGluR5 resulting in potentiating NMDA receptor activation and reversing NMDA receptor suppression induced by NMDA antagonists.
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dc.format.extent 3152460 bytes-
dc.format.mimetype application/pdf-
dc.language.iso en_US-
dc.relation (關聯) Journal of Biomedical Science,18(1), 19en_US
dc.title (題名) mGluR5 positive modulators both potentiate activation and restore inhibition in NMDA receptors by PKC dependent pathwayen_US
dc.type (資料類型) articleen
dc.identifier.doi (DOI) 10.1186/1423-0127-18-19en_US
dc.doi.uri (DOI) http://dx.doi.org/10.1186/1423-0127-18-19 en_US