Model-free and kinetic modelling approaches for characterising non-equilibrium pharmacological pathway activity: Internalisation of cannabinoid CB₁ receptors.

ABSTRACT:

Background and purpose

Receptor internalisation is by nature kinetic. Application of a standard equilibrium dose response model to describe the properties of a ligand inducing internalisation, while commonly used, are therefore problematic. Here, we propose two quantitative approaches to address this issue-(a) a model-free method and (b) a kinetic modelling approach-and systematically evaluate the performance of these methods against traditional equilibrium methods to characterise the internalisation profiles of cannabinoid CB₁ receptor agonists.

Experimental approach

Kinetic internalisation assays were conducted using a concentration series of six CB₁ receptor ligands. Internalisation rate analysis and snapshot equilibrium analysis were performed. A mo

SUBMITTER: Zhu X 

PROVIDER: S-EPMC6592866 | biostudies-literature | 2019 Jul

REPOSITORIES: biostudies-literature