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D1–D2 dopamine receptor heterooligomers with unique pharmacology are coupled to rapid activation of G q /11 in the striatum
Open accessAbstract
We demonstrate a heteromeric D1–D2 dopamine receptor signaling complex in brain that is coupled to G q /11 and requires agonist binding to both receptors for G protein activation and intracellular calcium release. The D1 agonist SKF83959 was identified as a specific agonist for the heteromer that activated G q /11 by functioning as a full agonist for the D1 receptor and a high-affinity partial agonist for a pertussis toxin-resistant D2 receptor within the complex. We provide evidence that the D1–D2 signaling complex can be more readily detected in mice that are 8 months in age compared with animals that are 3 months old, suggesting that calcium signaling through the D1–D2 dopamine receptor complex is relevant for function in the postadolescent brain. Activation of G q /11 through the heteromer increases levels of calcium/calmodulin-dependent protein kinase IIα in the nucleus accumbens, unlike activation of G s /olf-coupled D1 receptors, indicating a mechanism by which D1–D2 dopamine receptor complexes may contribute to synaptic plasticity.
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The molecular basis of CaMKII function in synaptic and behavioural memory
Lisman, J., Schulman, H., & Cline, H. (2002) · Nature Reviews Neuroscience · doi:10.1038/nrn753 · Cited by 1,860
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Klein, M. O., Battagello, D. S., Cardoso, A. R., Hauser, D. N., Bittencourt, J. C., & Correa, R. G. (2019) · Cellular and Molecular Neurobiology · doi:10.1007/s10571-018-0632-3 · Cited by 1,073
Kenakin, T., & Miller, L. J. (2010) · Pharmacological Reviews · doi:10.1124/pr.108.000992 · Cited by 573
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Beaulieu, J., Espinoza, S., & Gainetdinov, R. R. (2015) · British Journal of Pharmacology · doi:10.1111/bph.12906 · Cited by 521
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Metadata
- Authors
- Rashid, A. J., So, C. H., Kong, M. M. C., Furtak, T., El-Ghundi, M., Cheng, R., O'Dowd, B. F., & George, S. R.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 2007-01-09
- Volume
- 104
- Issue
- 2
- Pages
- 654-659
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2039482493
- Cited by
- 492
- References
- 1
- FWCI
- 10.68
- Type
- journal article
- Language
- en
- Open access
- bronze
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- CoChat. (2026). Citation check: D1–D2 dopamine receptor heterooligomers with unique pharmacology are coupled to rapid activation of G q /11 in the striatum. https://app.cochat.ai/papers/10.1073/pnas.0604049104
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- Rashid, A. J., So, C. H., Kong, M. M. C., Furtak, T., El-Ghundi, M., Cheng, R., O'Dowd, B. F., & George, S. R. (2007). D1–D2 dopamine receptor heterooligomers with unique pharmacology are coupled to rapid activation of G q /11 in the striatum. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.0604049104
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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