Abstract
Aim:
To elucidate the role of scaffold protein postsynaptic density (PSD)-95 in the dopamine D1 receptor (D1R)-modulated NR1a/NR2B receptor response.
Methods:
The human embryonic kidney 293 cells expressing D1R (tagged with the enhanced yellow fluorescent protein) and NR1a/NR2B with or without co-expression of PSD-95 were used in the experiments. The Ca2+ influx measured by imaging technique was employed to monitor N -methyl-D-aspartic acid receptors (NMDAR) function.
Results:
The application of dopamine (DA, 100 μmol/L) did not alter glutamate/glycine (Glu/Gly)-induced NMDAR-mediated Ca2+ influx in cells only expressing the D1R/NR1a/NR2B receptor. However, DA increased Glu/Gly-induced Ca2+ influx in a concentration-dependent manner while the cells were co-expressed with PSD-95. D1R-stimulated Ca2+ influx was inhibited by a selective D1R antagonist SCH23390. Moreover, pre-incubation with either the protein kinase A (PKA) inhibitor H89, or the protein kinase C (PKC) inhibitor chelerythrine attenuated D1R-enhanced Ca2+ influx induced by the N-methyl-D-aspartic acid (NMDA) agonist. The results clearly indicate that D1R-modulated NR1a/NR2B receptor function depends on PSD-95 and is subjected to the regulation of PKA and PKC.
Conclusion:
The present study provides the first evidence that PSD-95 is essential in D1R-regulated NR1a/NR2B receptor function.
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Project supported by the National Natural Science Foundation of China (No 30572168, 30672448) and the National 973 plan (No 2003CB5154000).
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Gu, Wh., Yang, S., Shi, Wx. et al. Requirement of PSD-95 for dopamine D1 receptor modulating glutamate NR1a/NR2B receptor function. Acta Pharmacol Sin 28, 756–762 (2007). https://doi.org/10.1111/j.1745-7254.2007.00557.x
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DOI: https://doi.org/10.1111/j.1745-7254.2007.00557.x