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

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 inter action 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 c ortex 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.

Source: Journal of Neurochemistry - April 12, 2020 Category: Neuroscience Authors: Hector E. Yarur, Marcela P. Gonz ález, Daniel Verbel‐Vergara, María E. Andrés, Katia Gysling Tags: ORIGINAL ARTICLE Source Type: research