Cross-talk between dopamine D1 and corticotropin releasing factor type 2 receptors leads to occlusion of their ERK1/2 signaling.
J Neurochem
; 155(3): 264-273, 2020 11.
Article
em En
| MEDLINE
| ID: mdl-32215915
One manner in which G protein-coupled receptors potentiate, increase, and change their functionality is through the formation of heteromers in a specific cellular context. Previously, we have shown that dopamine D1 receptor (D1R) and the corticotropin releasing factor receptor type-2α (CRF2α) heteromerize in HEK293T cells, enabling D1R to mobilize intracellular calcium in response to D1R agonists. In this study, we further investigated the pharmacological properties of the CRF2α-D1R heteromer and the consequences of the heteromerization in their signaling and subcellular localization when both receptors are co-expressed in HEK293T cells. Using immunoprecipitation assays, we observed that the addition of 10 µM dopamine in the incubation medium significantly decreased the amount of CRF2α on the cell surface of cells expressing both receptors. The presence of agonists of both receptors increased the interaction between CRF2α and D1R as assessed by co-immunoprecipitation. However, the presence of agonists of both receptors resulted in a lesser efficient activation of the mitogen-activated protein kinase/extracellular signal-regulated kinase. Using a synaptosomal preparation of rat prefrontal cortex devoid of post-synaptic elements, we found that CRF2α and D1R co-localize in synaptic terminals of the rat medial prefrontal cortex and that the simultaneous activation of both receptors also occluded phosphorylation of extracellular signal-regulated kinase. These results strengthen the idea that the heteromer CRF2a-D1R is an entity functionally different from each receptor that composes it and suggests that its formation is enhanced by CRF and dopamine co-transmission, as occurs in stress and addiction.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Receptores de Dopamina D1
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Receptores de Hormônio Liberador da Corticotropina
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Receptor Cross-Talk
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Sistema de Sinalização das MAP Quinases
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
J Neurochem
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
Chile
País de publicação:
Reino Unido