Corticotropin-releasing factor receptor 2 alpha (CRFR2α) (CRFR2α)

Corticotropin-releasing factor receptor 2 alpha (CRFR2α) is a specific splice variant of the CRFR2 protein, a member of the Class B G protein-coupled receptor family [1, 2]. In humans, the alpha isoform is the predominant form expressed in the central nervous system, particularly in regions like the hypothalamus and lateral septum, where it mediates stress recovery and modulates anxiety-related behaviors [3, 4]. Beyond the brain, CRFR2 is found in the heart, vasculature, and skeletal muscle, where it regulates cardiac contractility and protects against muscle atrophy [5, 6]. The receptor is primarily activated by the urocortin family of peptides (Urocortin 2 and 3), which show high selectivity for CRFR2 over the related CRFR1 [2, 5]. Pharmacological targeting of CRFR2α is of significant interest for treating acute heart failure due to its positive inotropic and lusitropic effects, as well as for managing muscle-wasting diseases [5, 6]. However, the therapeutic application is complicated by the receptor's diverse roles in the stress response and its potential to cause cardiovascular side effects like tachycardia [4, 7].

Other names

CRF-R2CRF2RCRH2RCorticotropin-releasing hormone receptor 2CRFR2 isoform alpha

Activation of the receptor by agonists triggers the Gs protein-mediated stimulation of adenylate cyclase, increasing intracellular cAMP levels and activating protein kinase A (PKA) and Epac signaling pathways [1, 2, 5].