Back to Search
Start Over
D1-D2 dopamine receptor heterooligomers with unique pharmacology are coupled to rapid activation of Gq/11 in the striatum.
- Source :
-
Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2007 Jan 09; Vol. 104 (2), pp. 654-9. Date of Electronic Publication: 2006 Dec 28. - Publication Year :
- 2007
-
Abstract
- We demonstrate a heteromeric D1-D2 dopamine receptor signaling complex in brain that is coupled to Gq/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 Gq/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 Gq/11 through the heteromer increases levels of calcium/calmodulin-dependent protein kinase IIalpha in the nucleus accumbens, unlike activation of Gs/olf-coupled D1 receptors, indicating a mechanism by which D1-D2 dopamine receptor complexes may contribute to synaptic plasticity.
- Subjects :
- Animals
Cell Line
Corpus Striatum drug effects
Dopamine Agonists pharmacology
Dopamine Antagonists pharmacology
Humans
Male
Mice
Mice, Knockout
Protein Structure, Quaternary
Rats
Rats, Sprague-Dawley
Receptors, Dopamine D1 deficiency
Receptors, Dopamine D1 genetics
Receptors, Dopamine D2 deficiency
Receptors, Dopamine D2 genetics
Signal Transduction
Corpus Striatum metabolism
GTP-Binding Protein alpha Subunits, Gq-G11 metabolism
Receptors, Dopamine D1 chemistry
Receptors, Dopamine D1 metabolism
Receptors, Dopamine D2 chemistry
Receptors, Dopamine D2 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 0027-8424
- Volume :
- 104
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Proceedings of the National Academy of Sciences of the United States of America
- Publication Type :
- Academic Journal
- Accession number :
- 17194762
- Full Text :
- https://doi.org/10.1073/pnas.0604049104