Biased Agonism of G Protein-Coupled Receptors: A Potential Therapeutic Strategy of Cardiovascular Diseases

Yun Hak Kim, Sae Ock Oh and Chi Dae Kim

G Protein-Coupled Receptors (GPCRs) are a family of seven transmembrane receptors, and are major targets of current clinical drugs. Many GPCRs have been successfully targeted by specific drugs which are classified as agonists or antagonists. Classically, the GPCR signal pathways are considered to be regulated by heterotrimeric G proteins. However, many researches have demonstrated that other molecules, β-arrestins, participate in the regulation of GPCRs associated intracellular signaling pathways. The major role of β-arrestins is to desensitize responses to G protein signals and to activate cytoplasmic molecules. GPCR ligands can dominantly activate either the G protein or β-arrestin pathway, which is the basis of the biased agonism of GPCR signaling. Both signals represent independent actions, for example, one is beneficial and the other is related to side effect. In this review, we summarize the signaling pathways of GPCRs and current biased agonist research on ligands with a focus on cardiovascular disease.