CRFR2

CRFR2 (corticotropin-releasing factor receptor 2, CRHR2) is a class B G protein-coupled receptor that mediates adaptive responses to physiological and psychological stress through selective interactions with the urocortin peptide family^[1][2]. Mechanistically, CRFR2 regulates stress-recovery signaling, autonomic function, emotional processing, and neuroendocrine homeostasis through downstream G protein-dependent pathways that influence CREB phosphorylation and cellular stress responses^[3][4]. In experimental models, genetic deletion of Crhr2 produces enhanced anxiety-like behavior, stress hypersensitivity, and impaired adaptation to environmental challenges, establishing CRFR2 as a key regulator of stress resilience rather than stress initiation^[3][4][5]. Compared with the closely related isoform CRFR1, which predominantly promotes anxiogenic and hypothalamic-pituitary-adrenal axis activation, CRFR2 exerts counter-regulatory functions that facilitate recovery from stress exposure and restoration of homeostasis^[2][3][5]. The receptor also displays distinct isoform diversity, including CRFR2α, CRFR2β, and CRFR2γ, which differ in N-terminal structure, tissue distribution, and ligand responsiveness, providing additional regulatory specificity for experimental studies of receptor signaling^[6][7]. For research applications, the endogenous agonists urocortin II and urocortin III exhibit high selectivity for CRFR2 and are widely used to investigate receptor-dependent stress, cardiovascular, metabolic, and behavioral pathways in vivo and in vitro^[1][2].