Corticotropin-releasing factor receptors 1 and 2 (CRF1R/CRF2R)

Corticotropin-releasing factor receptor 1 and corticotropin-releasing factor receptor 2 (CRF1R and CRF2R) are members of the G protein-coupled receptor (GPCR) superfamily, specifically within the secretin-like (class B1) family[1][5]. They bind corticotropin-releasing factor and related peptides (urocortins), orchestrating the central and peripheral stress response by activating signaling pathways (primarily via cAMP/PKA and IP3/DAG), leading to changes in gene expression and hormone release, especially regulation of the hypothalamic-pituitary-adrenal (HPA) axis[4][6][8]. CRF1R initiates the stress response, primarily in the brain and pituitary, whereas CRF2R modulates and can resolve these responses, with outputs that affect behavior, immunity, metabolism, and neuroplasticity[4][6][7][3]. Dysregulation or genetic variants in these receptors are implicated in psychiatric disorders such as anxiety, depression, PTSD, and addiction, making them investigated targets for CNS drug discovery[4][5][6]. Both receptors are widely and differentially expressed in the brain and peripheral tissues, with diverse splice variants and specific peptide ligand affinities[3][8].

Other names

Corticotropin-releasing hormone receptor 1 (CRHR1)Corticotropin-releasing hormone receptor 2 (CRHR2)CRF receptor type 1 (CRF1R)CRF receptor type 2 (CRF2R)Corticotropin-releasing factor receptor type 1Corticotropin-releasing factor receptor type 2Secretin family receptors (class B1 GPCRs; as a family classification)

Antagonists block receptor activation, dampening stress-induced signaling. Agonists (CRF, urocortins) activate receptor, upregulating cAMP, PKC, and downstream gene transcription. Allosteric modulation by small molecules (under investigation).