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| Content Provider | World Health Organization (WHO)-Global Index Medicus |
|---|---|
| Author | Galaz, P. Campusano, J. M. Ciruela, F. Slater, P. G. Araya, K. A. Gysling, K. Fuenzalida, J. Blanco, E. H. |
| Description | Author Affiliation: Fuenzalida J ( Millennium Nucleus in Stress and Addiction, Department of Cellular and Molecular Biology, Faculty of Biological Sciences, Pontificia Universidad Católica de Chile, Santiago, Chile.) |
| Abstract | BACKGROUND AND PURPOSE: Dopamine and corticotrophin-releasing hormone (CRH; also known as corticotrophin-releasing factor) are key neurotransmitters in the interaction between stress and addiction. Repeated treatment with cocaine potentiates glutamatergic transmission in the rat basolateral amygdala/cortex pathway through a synergistic action of D1 -like dopamine receptors and CRH type-2 receptors (CRF2 receptors). We hypothesized that this observed synergism could be instrumented by heteromers containing the dopamine D1 receptor and CRF2 receptor. EXPERIMENTAL APPROACH: D1 /CRF2 receptor heteromerization was demonstrated in HEK293T cells using co-immunoprecipitation, BRET and FRET assays, and by using the heteromer mobilization strategy. The ability of D1 receptors to signal through calcium, when singly expressed or co-expressed with CRF2 receptors, was evaluated by the calcium mobilization assay. KEY RESULTS: D1 /CRF2 receptor heteromers were observed in HEK293T cells. When singly expressed, D1 receptors were mostly located at the cell surface whereas CRF2 receptors accumulated intracellularly. Interestingly, co-expression of both receptors promoted D1 receptor intracellular and CRF2 receptor cell surface targeting. The heteromerization of D1 /CRF2 receptors maintained the signalling through cAMP of both receptors but switched D1 receptor signalling properties, as the heteromeric D1 receptor was able to mobilize intracellular calcium upon stimulation with a D1 receptor agonist. CONCLUSIONS AND IMPLICATIONS: D1 and CRF2 receptors are capable of heterodimerization in living cells. D1 /CRF2 receptor heteromerization might account, at least in part, for the complex physiological interactions established between dopamine and CRH in normal and pathological conditions such as addiction, representing a new potential pharmacological target. |
| ISSN | 00071188 |
| e-ISSN | 14765381 |
| Journal | British Journal of Pharmacology |
| Issue Number | 24 |
| Volume Number | 171 |
| Language | English |
| Publisher | Wiley Online Library(on behalf of The British Pharmacological Society) |
| Publisher Date | 2014-12-01 |
| Publisher Place | Great Britain (UK) |
| Access Restriction | Open |
| Subject Keyword | Cell Membrane Metabolism Receptors, Corticotropin-Releasing Hormone Receptors, Dopamine D1 Calcium Corticotropin-Releasing Hormone Dopamine HEK293 Cells Immunoprecipitation Signal Transduction Research Support, Non-U.S. Gov't Pharmacology |
| Content Type | Text |
| Resource Type | Article |
| Subject | Pharmacology |
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