Corticotropin-releasing factor receptor 2 (CRF-R2) (CRF-R2)

Corticotropin-releasing factor receptor 2 (CRF-R2) is a Class B G protein-coupled receptor that serves as a key mediator in the physiological response to stress and the regulation of homeostatic processes [UniProt: Q13324]. While its sister receptor, CRF-R1, is primarily responsible for the immediate activation of the hypothalamic-pituitary-adrenal (HPA) axis, CRF-R2 is involved in the counter-regulatory and recovery phases of the stress response [PubMed: 15505535]. It is activated by the urocortin family of peptides (Ucn 1, 2, and 3), with Ucn 2 and 3 showing high selectivity for this receptor over CRF-R1 [IUPHAR: CRF2 receptor]. CRF-R2 is expressed in both the central nervous system—regulating anxiety, appetite, and mood—and in peripheral tissues such as the heart, vasculature, and skeletal muscle [PubMed: 22438212]. In the cardiovascular system, CRF-R2 activation induces potent vasodilation and positive inotropic effects, leading to its investigation as a therapeutic target for acute heart failure [PubMed: 20633453]. Additionally, its role in modulating gastrointestinal motility and skeletal muscle mass has made it a focus for treating irritable bowel syndrome and muscle wasting disorders [PubMed: 12660313]. Pharmacological modulation of CRF-R2 includes the use of selective agonists for cardiovascular benefits and antagonists for potential psychiatric or gastric applications [PubMed: 22438212]. Despite its therapeutic potential, clinical development has been hindered by the complexity of its systemic effects and the need for precise tissue targeting [PubMed: 20633453].

Other names

CRHR2CRF2Corticotropin-releasing hormone receptor 2CRF-R-2HM-CRF

Agonism of the receptor leads to Gs-protein coupling, activating adenylyl cyclase and increasing intracellular cAMP levels; Antagonism blocks the binding of endogenous urocortins to prevent receptor-mediated signaling [PubMed: 22438212].