Cannabinoid GPCR Assays
Overview of Cannabinoid Receptors
Cannabinoid receptors are a family of GPCRs that play a critical role in physiology, with two major subtypes, CB1 and CB2. CB1 is mainly expressed in central and peripheral neurons while CB2 exists primarily in the immune system. Both receptor types are coupled via G proteins to adenylyl cyclase and mitogen-activated protein kinase. Meanwhile, these receptors are attractive targets for many diseases.
Fig.1. Schematic model of CB1 and CB2 and related intracellular signaling pathways. (Ye, 2019)
Functions of Receptors
Cannabinoid receptors have been receiving extensive attention in drug development. Considerable evidence has demonstrated that the pharmacological modulation of CB1 has critical potential in the treatment of various diseases, such as obesity, inflammation, pain, neurodegenerative diseases, and cancer. CB2 is a promising therapeutic target for pain management, immunomodulators, osteoporosis, and liver disease therapy.
Recently, scientists discovered that apart from CB1 and CB2, there are other cannabinoid-related orphan GPCRs, such as GPR18, GPR55, and GPR119. The relevant information and mechanisms of these receptors are listed in the table.
| Receptor | Gene | Mechanism | Agonists | Antagonists |
| CB1 receptor | CNR1 |
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| CB2 receptor | CNR2 |
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| GPR55 receptorr | GPR55 |
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Assay List of Cannabinoid Receptors
Creative Biolabs can provide a range of assays of cannabinoid receptors. You can choose the assay in the list or contact us for more information:
Published Data
| Paper Title | Control of glutamate release by complexes of adenosine and cannabinoid receptors |
| Journal | BMC Biology |
| Published | 2020 |
| Abstract | Heteromerization of the adenosine A2A receptor (A2AR) and the cannabinoid CB1 receptor (CB1R) may be involved in the integration of adenosine and endocannabinoid signaling that regulates striatal excitatory neurotransmission. A2AR-CB1R heteromers have been demonstrated in artificial cell systems. One of the main biochemical features of A2AR signaling is the dependence on Gi protein-mediated CB1R signaling. Recently, the localization of the A2AR-CB1R heteromer at the striatal glutamatergic terminus has attracted much attention. |
| Result |
The researchers established the A2AR-CB1R tetrameric structure using a peptide interference method in combination with techniques and models in mammalian transfected cells. The specific quaternary structure of A2A-CB1R has been implicated in intermolecular interactions involving the long C-terminus of A2AR. The researchers demonstrated the presence of A2AR-CB1R heteromers with the same characteristics as those studied in mammalian transfected cells by using heteromeric interfering peptides in striatal glutamatergic end experiments. First, A2AR agonists or A2AR antagonists allosterically counteract Gi-mediated inhibition of glutamate release. Second, the co-administration of A2AR agonists and antagonists counteracted the effects of each other. Finally, CB1R agonists inhibited the constitutive activation of A2AR, thereby inhibiting glutamate release.
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Fig.2. Modulation by A2AR ligands on CB1R-mediated G protein activation in the A2AR-CB1R heteromer. (Köfalvi, 2020)
References
- Ye, L.; et al. New insights in cannabinoid receptor structure and signaling. Current molecular pharmacology. 2019; 12(3): 239.
- Köfalvi, A.; et al. Control of glutamate release by complexes of adenosine and cannabinoid receptors. BMC biology. 2020; 18(1): 1-21.
