Corticotropin-releasing factor receptor 2 gamma (CRFR2γ)

Corticotropin-releasing factor receptor 2 gamma (CRFR2γ) is a human-specific splice variant of the CRFR2 G protein-coupled receptor, primarily localized in the central nervous system, specifically within the septum and hippocampus (Kostich et al., 2001, Molecular Endocrinology). As a member of the Class B secretin-like GPCR family, it plays a pivotal role in the late-stage stress response and the maintenance of emotional and physiological homeostasis (Hauger et al., 2003, Pharmacological Reviews). The receptor is preferentially activated by urocortins 1, 2, and 3, which exhibit higher affinity for CRFR2 than the primary stress hormone, corticotropin-releasing factor (CRF) (Hillhouse & Grammatopoulos, 2006, Endocrine Reviews). In clinical contexts, CRFR2γ is linked to the pathophysiology of anxiety, depression, and stress-related gastrointestinal disorders. Therapeutic strategies targeting this receptor aim to modulate these pathways, though development is complicated by the receptor's diverse physiological roles, including its influence on cardiovascular function and thermogenesis (Bale & Vale, 2004, Annual Review of Pharmacology and Toxicology). Consequently, while it remains a promising target for neuropsychiatric and metabolic conditions, ensuring tissue-specific activity is a significant hurdle for drug safety.

Other names

CRF2R gammaCRH2R gammaCorticotropin-releasing hormone receptor 2 isoform gammaCRF-R2 gammaCRHR2 gamma

Agonist binding triggers Gs-protein coupling, activating adenylate cyclase and increasing intracellular cAMP levels.