Somatostatin receptor 5 is a prominent regulator of signaling pathways in cells with coexpression of Cannabinoid receptors 1.

Endocannabinoids and somatostatin play critical roles in several pathophysiological conditions via binding to different receptor subtypes. Cannabinoid receptor 1 (CB1R) and somatostatin receptors are expressed in several brain regions and share overlapping functions. Whether these two prominent members of G-protein-coupled receptor (GPCR) family interact with each other and constitute a functional receptor complex is not known. In the present study, we investigated the colocalization of CB1R and in rat brain, and studied receptor internalization, interaction and signal transduction pathways in HEK-293 cells cotransfected with human cannabinoid receptor 1 (hCB1R) and Our results showed that CB1R and duanyu1942R5 colocalized in rat brain cortex, striatum, and hippocampus. CB1R was expressed in duanyu1942R5 immunoprecipitate prepared from the brain tissue lysate, indicating their association in a system where these receptors are endogenously expressed. In cotransfected HEK-293 cells, duanyu1942R5 and CB1R existed in a constitutive heteromeric complex under basal condition, which was disrupted upon agonist treatments. Furthermore, concurrent receptor activation led to preferential formation of duanyu1942R5 homodimer and dissociation of CB1R homodimer. We also discovered that second messenger cyclic adenosine monophosphate and downstream signaling pathways were modulated in a and concentration-dependent manner in the presence of receptor-specific agonist. In conclusion, with predominant role of the functional consequences of crosstalk between duanyu1942R5 and CB1R resulting in the regulation of receptor trafficking and signal transduction pathways open new therapeutic avenue in cancer biology and excitotoxicity.

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