Crosstalk between dopamine D1 and corticotropin releasing factor type 2 receptors leads to occlusion of their ERK1/2 signaling

AbstractOne 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 HEK293 T cells, enabling D1R to mobilize intracellular calcium in response to D1R agonists. In the present 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 recep tors 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 increa sed 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 (ERK). Using a synaptosomal preparation of rat prefrontal cortex devoid of postsynaptic elements, we found that CRF2α and D1R colocalize in synaptic terminals of the rat medial prefrontal cortex and that the simultaneous activation of both receptors also occluded phosphorylation of ERK. These results stre...
Source: Journal of Neurochemistry - Category: Neuroscience Authors: Tags: ORIGINAL ARTICLE Source Type: research