Characterization of novel cannabinoid ligands and receptor-receptor interactions with a focus on the type 2 cannabinoid receptor
| dc.contributor.advisor | Laprairie, Robert | |
| dc.contributor.committeeMember | Alcorn, Jane | |
| dc.contributor.committeeMember | Badea, Ildiko | |
| dc.contributor.committeeMember | Lukong, Erique | |
| dc.creator | Mohamed, Kawthar A | |
| dc.date.accessioned | 2023-03-31T22:11:15Z | |
| dc.date.available | 2023-03-31T22:11:15Z | |
| dc.date.copyright | 2023 | |
| dc.date.created | 2023-03 | |
| dc.date.issued | 2023-03-31 | |
| dc.date.submitted | March 2023 | |
| dc.date.updated | 2023-03-31T22:11:15Z | |
| dc.description.abstract | Cannabis and cannabinoids are currently being investigated for their potential utility as therapeutics in various illnesses. Of the two cannabinoid receptors that have been identified thus far, the type 2 cannabinoid receptor (CB2R) is of growing interest due to its potential immunomodulatory and anti-inflammatory activities. Similarly, the orphan receptor G protein-coupled receptor 55 (GPR55) is known to interact with cannabinoids and has potential for its anti-inflammatory activity. CB2R- and GPR55-mediated therapeutics may provide safer side effect profiles and avoid central nervous system (CNS)-mediated psychoactivity associated with the activation of the type 1 cannabinoid receptor (CB1R). The identification of CB2R-specific ligands has been challenging given the high degree of similarity between CB1R and CB2R. Exploiting novel paradigms in G protein-coupled receptor (GPCR) signaling, such as biased agonism, bitopic ligands, and receptor dimerization, may provide a new avenue for the development of clinically effective CB2R-selective ligands. Characterizing a diverse array of ligands, including orthosteric agonists, allosteric modulators, bitopic ligands, and compound metabolites may improve our ability to identify novel drug candidates. In this study, we explored the in vitro pharmacological properties of novel GPR55 and CB2R ligands, cannabinoid-orexin receptor heterodimers and phytocannabinoid metabolites using Chinese hamster ovary (CHO)-K1 cells expressing human CB1R, CB2R, GPR55, orexin receptor type 1 (OX1R), or orexin receptor type 2 (OX2R) plasmids. Our study revealed that novel cannabinoids can be characterized using pharmacological data and drug design. Relatively little is known about the specific pharmacological properties and mechanisms of ligands and receptor interactions at CB2R. A better understanding of these pharmacodynamics may be useful in the development of CB2R-selective therapeutics for illnesses associated with inflammation and/or pain. | |
| dc.format.mimetype | application/pdf | |
| dc.identifier.uri | https://hdl.handle.net/10388/14543 | |
| dc.language.iso | en | |
| dc.subject | Cannabinoids | |
| dc.subject | Cannabinoid receptors | |
| dc.subject | Orexin receptors | |
| dc.subject | G protein-coupled receptors | |
| dc.subject | Bitopic ligands | |
| dc.subject | Biased agonism | |
| dc.subject | Receptor dimerization | |
| dc.subject | Phytocannabinoid metabolites | |
| dc.title | Characterization of novel cannabinoid ligands and receptor-receptor interactions with a focus on the type 2 cannabinoid receptor | |
| dc.type | Thesis | |
| dc.type.material | text | |
| thesis.degree.department | Pharmacy and Nutrition | |
| thesis.degree.discipline | Pharmacy | |
| thesis.degree.grantor | University of Saskatchewan | |
| thesis.degree.level | Masters | |
| thesis.degree.name | Master of Science (M.Sc.) |