Biased agonism

When a ligand binds to a receptor, more than one pathway can be activated. Activation of these signal transduction pathways can vary, depending on the agonist that binds. Biased agonism describes the phenomenon that a ligand can bind to a receptor and activates one of several signalling pathways, whereas another agonist acting on the same receptor activates another pathway. Thus, several agonists that act at the same receptor can initiate diverse cellular outcomes. To which extent these different pathways are activated is ligand depending. Biased agonism is mostly described for – but not restricted to - G protein coupled receptors (GPCRs).

The rationale behind different responses to different ligands is based that each ligand induces a specific conformation change of the receptor. In example, one can understand that (slight) changes in the conformation of a GPCR, will also differentially affect downstream activation (2nd messengers or arrestin pathways).