Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
5737540 | Neuroscience | 2017 | 14 Pages |
Abstract
Endocannabinoids and somatostatin (SST) play critical roles in several pathophysiological conditions via binding to different receptor subtypes. Cannabinoid receptor 1 (CB1R) and somatostatin receptors (SSTRs) 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 SSTR5 in rat brain, and studied receptor internalization, interaction and signal transduction pathways in HEK-293 cells cotransfected with human cannabinoid receptor 1 (hCB1R) and hSSTR5. Our results showed that CB1R and SSTR5 colocalized in rat brain cortex, striatum, and hippocampus. CB1R was expressed in SSTR5 immunoprecipitate prepared from the brain tissue lysate, indicating their association in a system where these receptors are endogenously expressed. In cotransfected HEK-293 cells, SSTR5 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 SSTR5 homodimer and dissociation of CB1R homodimer. We also discovered that second messenger cyclic adenosine monophosphate and downstream signaling pathways were modulated in a SSTR5-dominant and concentration-dependent manner in the presence of receptor-specific agonist. In conclusion, with predominant role of SSTR5, the functional consequences of crosstalk between SSTR5 and CB1R resulting in the regulation of receptor trafficking and signal transduction pathways open new therapeutic avenue in cancer biology and excitotoxicity.
Keywords
Cy3CB1RPTXforskolinGPCRD2RpKaPAGEFskSSTSSTRsFITCIBMXPI3Ksomatostatin receptor 53-isobutyl-1-methylxanthinecAMPERK1/2Cyclic adenosine monophosphatepolyacrylamide gel electrophoresisAlzheimer’s diseaseHuntington’s diseaseCNSSomatostatinCyanine 3central nervous systemSignalingCo-IPphosphoinositide-3 kinasefluorescein isothiocyanateHeterodimerizationCo-Immunoprecipitationhemagglutininprotein kinase Aextracellular signal-regulated kinase 1/2dopamine receptor 2Somatostatin receptorsCannabinoid receptor 1G protein-coupled receptor
Related Topics
Life Sciences
Neuroscience
Neuroscience (General)
Authors
Shenglong Zou, Rishi K. Somvanshi, Ujendra Kumar,