Requirement of PSD-95 for dopamine D<sub>1</sub>receptor modulating glutamate NR1a/NR2B receptor function

Gu, Wei-hua; Shen, Yang; Shi, Wei‐Xing; Jin, Guo-Zhang; Zhen, Xuechu

doi:10.1111/j.1745-7254.2007.00557.x

Cited by 26 publications

(23 citation statements)

References 17 publications

(27 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…It may be suggested that the inhibition induced by Hal or the Cloz D 2 R blockade is the result of the inhibitory effect on the PFC NMDAR; subsequently, the inhibition would deteriorate the therapeutic effect, based on the DA function imbalance hypothesis [1,2] . As to the indirect interaction between SPD and NMDAR, we obtained definite evidence requiring postsynaptic density-95 (PSD-95) [21] . In an in vitro study, when PSD-95 was co-expressed with D 1 R and NMDAR in HEK293 cells, the activation of D 1 R could enhance NMDAR-mediated Ca 2+ influx [21] .…”

Section: Discussionmentioning

confidence: 85%

“…As to the indirect interaction between SPD and NMDAR, we obtained definite evidence requiring postsynaptic density-95 (PSD-95) [21] . In an in vitro study, when PSD-95 was co-expressed with D 1 R and NMDAR in HEK293 cells, the activation of D 1 R could enhance NMDAR-mediated Ca 2+ influx [21] . SPD hence could not display its enhancing effect on NMDAR under such experimental conditions without PSD-95.…”

Section: Discussionmentioning

confidence: 85%

“…Therefore, the different effects of the 3 drugs on NMDAR function may imply that SPD, Hal, and Cloz have different mechanisms in its antipsychotic use. In other words, Hal and Cloz have direct interaction with NMDAR, while SPD has an indirect one [21] . Our results showed that the significant inhibitory effect on Ca 2+ influx by Hal was observed at 0.1 µmol/L, while Cloz was at 1 µmol/L.…”

Section: Discussionmentioning

confidence: 99%

“…It is presumed that the modulatory effect of SPD on NMDAR function is an indirect effect via the D 1 R [16,21] .…”

Section: Discussionmentioning

confidence: 99%

See 3 more Smart Citations

Effects of (-)-stepholidine on NMDA receptors: comparison with haloperidol and clozapine

Shen

Shi

et al. 2007

Acta Pharmacologica Sinica

Self Cite

View full text Add to dashboard Cite

Aim: To examine whether (-)-stepholidine (SPD) has a direct effect on the Nmethyl-D-aspartic acid receptors (NMDAR) containing the NMDA receptor subunits NR2A or NR2B and to compare its effect with those of haloperidol (Hal) and clozapine (Cloz). Methods: NMDAR was transiently expressed in human embryonic kidney 293 (HEK293) cells. Changes in intracellular calcium concentration ([Ca 2+ ] i ) induced by NMDAR activation were monitored with Fura-2 ratio imaging techniques. Results: SPD had no significant effects on either subunit of NMDAR at a concentration of less than 100 µmol/L. Hal selectively inhibited NMDAR containing the NR2B subunit, whereas Cloz inhibited both subunits of NMDAR. Although both Hal and Cloz inhibited NR1a/NR2B receptor-mediated Ca 2+ influx, their effects were different. Hal was more potent and had a faster peak effect than Cloz. Conclusion: Both Hal and Cloz inhibit NMDAR-mediated function, whereas SPD produced only a little inhibition at a high concentration. Based on our other studies, the modulation of SPD on NMDAR function may be via D 1 receptor action underlying an indirect mechanism.

show abstract

Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 85%

Section: Discussionmentioning

confidence: 99%

“…It is presumed that the modulatory effect of SPD on NMDAR function is an indirect effect via the D 1 R [16,21] .…”

Section: Discussionmentioning

confidence: 99%

See 2 more Smart Citations

Effects of (-)-stepholidine on NMDA receptors: comparison with haloperidol and clozapine

Shen

Shi

et al. 2007

Acta Pharmacologica Sinica

Self Cite

View full text Add to dashboard Cite

show abstract

“…For example, dopamine increases NMDAR-mediated calcium influx in a PSD-95-dependent manner, 238 further supporting the role of PSD-95 as a scaffold linking various signaling pathways. In the nucleus accumbens, the dopamineinduced increase in NMDAR-mediated calcium influx is mediated by PKA and PKC and can be reversed by activity of the pathway of dopamine-and cAMP-regulated phosphoprotein (DARPP-32; M r 32 kD) and PP-1, 239 indicating that the effect of dopamine is mediated through phosphorylation.…”

Section: Modulation Of Nmda Receptors By Other Receptorsmentioning

confidence: 92%

Trafficking and Targeting of NMDA Receptors

Petralia¹,

Wenthold²,

Al‐Hallaq³

2008

Biology of the NMDA Receptor

View full text Add to dashboard Cite

Calcium-Dependent Networks in Dopamine–Glutamate Interaction: The Role of Postsynaptic Scaffolding Proteins

Bartolomeis¹,

Tomasetti²

2012

Mol Neurobiol

View full text Add to dashboard Cite

Dopamine and glutamate systems are both involved in cognitive, behavioral, and motor processes. Dysfunction of dopamine-glutamate interplay has been suggested in several psychotic diseases, above all in schizophrenia, for which there exists a need for novel medications. Intracellular calcium-dependent transduction pathways are key determinants of dopamine-glutamate interactions, which take place mainly, albeit not exclusively, in the postsynaptic density (PSD), a highly specialized postsynaptic ultrastructure. Stimulation of dopamine and glutamate receptors modulates the gene expression and the function of specific PSD proteins, the "scaffolding" proteins (Homer, Shank, and PSD95), belonging to a complex Ca(2+)-regulated network that integrates and converges dopamine and glutamate signaling to appropriate nuclear targets. Dysfunction of scaffolding proteins leads to severe impairment of Ca(2+)-dependent signaling, which may underlie the dopamine-glutamate aberrations putatively implicated in the pathogenesis of psychotic disorders. Antipsychotic therapy has been demonstrated to directly and indirectly affect the neuronal Ca(2+)-dependent pathways through the modulation of PSD scaffolding proteins, such as Homer, therefore influencing both dopaminergic and glutamatergic functions and enforcing Ca(2+)-mediated long-term synaptic changes. In this review, we will discuss the role of PSD scaffolding proteins in routing Ca(2+)-dependent signals to the nucleus. In particular, we will address the implication of PSD scaffolding proteins in the intracellular connections between dopamine and glutamate pathways, which involve both Ca(2+)-dependent and Ca(2+)-independent mechanisms. Finally, we will discuss how new strategies for the treatment of psychosis aim at developing antipsychotics that may impact both glutamate and dopamine signaling, and what should be the possible role of PSD scaffolding proteins.

show abstract

Requirement of PSD-95 for dopamine D₁receptor modulating glutamate NR1a/NR2B receptor function

Abstract: The present study provides the first evidence that PSD-95 is essential in D1R-regulated NR1a/NR2B receptor function.

Cited by 26 publications

References 17 publications

Effects of (-)-stepholidine on NMDA receptors: comparison with haloperidol and clozapine

Effects of (-)-stepholidine on NMDA receptors: comparison with haloperidol and clozapine

Trafficking and Targeting of NMDA Receptors

Calcium-Dependent Networks in Dopamine–Glutamate Interaction: The Role of Postsynaptic Scaffolding Proteins

Contact Info

Product

Resources

About

Requirement of PSD-95 for dopamine D1receptor modulating glutamate NR1a/NR2B receptor function

Abstract: The present study provides the first evidence that PSD-95 is essential in D1R-regulated NR1a/NR2B receptor function.

Cited by 26 publications

References 17 publications

Effects of (-)-stepholidine on NMDA receptors: comparison with haloperidol and clozapine

Effects of (-)-stepholidine on NMDA receptors: comparison with haloperidol and clozapine

Trafficking and Targeting of NMDA Receptors

Calcium-Dependent Networks in Dopamine–Glutamate Interaction: The Role of Postsynaptic Scaffolding Proteins

Contact Info

Product

Resources

About

Requirement of PSD-95 for dopamine D₁receptor modulating glutamate NR1a/NR2B receptor function