- 作者: Hwei-Hsien Chen; Pei-Fei Liao; Ming-Huan Chan
- 作者服務機構: Institute of Pharmacology and Toxicology, Tzu Chi University, Taiwan, R.O.C.
- 中文摘要: --
- 英文摘要:
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. - 中文關鍵字: --
- 英文關鍵字: Ketamine, mGluR5, NMDA, Field potential, Hippocampus, PKC