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Aim:To elucidate the role of scaffold protein postsynaptic density (PSD)-95 inthe dopamine D_1 receptor (D_1R)-modulated NR1a/NR2B receptor response.Methods:The human embryonic kidney 293 cells expressing D_1R (tagged with theenhanced yellow fluorescent protein) and NR1a/NR2B with or without co-expres-sion of PSD-95 were used in the experiments.The Ca~(2+) influx measured by imagingtechnique was employed to monitor N-methyl-D-aspartic acid receptors (NMDAR)function.Results:The application of dopamine (DA,100 μmol/L) did not alterglutamate/glycine (Glu/Gly)-induced NMDAR-mediated Ca~(2+)influx in cells onlyexpressing the D_1R/NR1a/NR2B receptor.However,DA increased Glu/Gly-induced Ca~(2+)influx in a concentration-dependent manner while the cells wereco-expressed with PSD-95.D_1R-stimulated Ca~(2+)influx was inhibited by a selectiveD_1R antagonist SCH23390.Moreover,pre-incubation with either the proteinkinase A (PKA) inhibitor H89,or the protein kinase C (PKC) inhibitor chelerythrineattenuated D_1R-enhanced Ca~(2+)influx induced by the N-methyl-D-aspartic acid(NMDA) agonist.The results clearly indicate that D_1R-modulated NR1a/NR2Breceptor function depends on PSD-95 and is subjected to the regulation of PKAand PKC.Conclusion:The present study provides the first evidence that PSD-95is essential in D_1R-regulated NR1a/NR2B receptor function.
Aim: To elucidate the role of scaffold protein postsynaptic density (PSD) -95 inthe dopamine D_1 receptor (D_1R) -modulated NR1a / NR2B receptor response. Methods: The human embryonic kidney 293 cells expressing D_1R (tagged with the enhanced yellow fluorescent protein) and NR1a / NR2B with or without co-expres-sion of PSD-95 were used in the experiments. Ca 2+ 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 Ca 2+ influx in cells only express the the D_1R / NR1a / NR2B receptor. increased Glu / Gly-induced Ca ~ (2+) influx in a concentration-dependent manner while the cells were co-expressed with PSD-95. D1R-stimulated Ca ~ (2+) influx was inhibited by a selective D1R antagonist SCH23390. pre-incubation with either the proteinkinase A (PKA) inhibitor H89, or the protein kinase C (PKC) inhibitor chelerythrineatt enuated D 1 -R-enhanced Ca 2+ influx induced by the N-methyl-D-aspartic acid (NMDA) agonist. The results clearly identify that D 1 R-modulated NR 1 a / NR 2 B receptor function depends on PSD-95 and is subjected to the regulation of PKAand PKC.Conclusion: The present study provides the first evidence that PSD-95is essential in D-1R-regulated NR1a / NR2B receptor function.