Evaluation of the profiles of CB
Biased agonism describes the ability of ligands to differentially regulate multiple signalling pathways when coupled to a single receptor. Signalling is affected by rapid agonist-induced receptor internalisation. Hence, the conventional use of equilibrium models may not be optimal, because (i) receptor numbers vary with time and, in addition, (ii) some pathways may show non-monotonic profiles over time. Data were available from internalisation, cAMP inhibition and phosphorylation of ERK (pERK) of the cannabinoid-1 (CB A joint kinetic model was able to capture the signalling profiles across all pathways for the CB This is the first joint kinetic assessment of biased agonism at a GPCR (e.g. CB