Comparison of Agonist Activity between CB1 and CB2 Receptors with Orthosteric Site Mutations.

ABSTRACT: Human endocannabinoid signaling is primarily mediated by the cannabinoid receptors, CB1 and CB2, which are G protein-coupled receptors (GPCRs). These receptors have been linked to a variety of physiological processes and are being pursued as prospective drug targets due to their potential in treating pain and inflammation. However, because of their homology and shared signaling mechanisms, investigating the individual physiological roles of these receptors and designing subtype-selective ligands has been challenging. Using active-state CB1 and CB2 structures as guides, homologous residues within the orthosteric pocket of each receptor were mutated to alanine to test whether they equally impair CB1 and CB2 activity in response to two high-affinity, nonselective agonists (CP55,940 and AM1203

SUBMITTER: Brust CA 

PROVIDER: S-EPMC12080992 | biostudies-literature | 2024 Sep

REPOSITORIES: biostudies-literature