Evaluation of the profiles of CB₁ cannabinoid receptor signalling bias using joint kinetic modelling.

ABSTRACT:

Background and purpose

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.

Experimental approach

Data were available from internalisation, cAMP inhibition and phosphorylation of ERK (pERK) of the cannabinoid-1 (CB₁ ) receptor using a concentration series of six CB₁ ligands (CP55,940, WIN55,212-2, anandamide, 2-arachidonylglycerol, Δ⁹ -tetrahydrocannabinol and BAY59,3074). The joint kinetic mode

SUBMITTER: Zhu X 

PROVIDER: S-EPMC7369624 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature