AGTR2

AGTR2, or the Angiotensin II receptor type 2, is a G protein-coupled receptor of the renin–angiotensin system. It binds angiotensin II with lower affinity than the type 1 receptor and is often described as mediating effects that oppose AT1 receptor activation, including vasodilation and anti-proliferative actions. The receptor is encoded by the AGTR2 gene.

The AGTR2 gene is located on the X chromosome (Xq28). Expression patterns vary by tissue and developmental stage, with high levels in fetal tissues and notable presence in brain, kidney, heart, vasculature, and adrenal glands. In adults, expression is more restricted but retained in several organs; species differences exist.

Signaling and physiological roles: AGTR2 signals through Gi/o proteins and may engage beta-arrestin pathways; it can stimulate the production of nitric oxide and cyclic GMP, contributing to vasodilation and anti-inflammatory effects. It also exhibits anti-fibrotic and anti-proliferative actions and can promote tissue repair. In development, AGTR2 contributes to normal fetal kidney and brain maturation; in adults, it can counterbalance AT1 receptor–mediated responses.

Clinical relevance: Preclinical studies have explored selective AT2 receptor agonists, such as C21, for neuroprotection, anti-fibrotic therapy, and ischemia–reperfusion injury; progress toward clinical use has been limited. Changes in AGTR2 expression or signaling have been reported in various diseases, and genetic variation in AGTR2 has been investigated for associations with cardiovascular traits, with inconsistent findings.