CRHR1

G protein-coupled receptor for CRH and UCN stress hormones, which plays a central role in whole body adaptation to stress. Ligand binding causes a conformation change that triggers signaling via guanine nucleotide-binding proteins (G proteins) and downstream effectors, such as adenylate cyclase. CRHR1 is mainly coupled to G(s) G protein (GNAS), mediating activation of adenylate cyclase activity and production of cAMP. In some conditions, can also couple to G(q) G protein (GNAQ) and mediate production of diacylglycerol (DAG) and inositol 1,4,5-trisphosphate (IP3) second messengers. CRHR1-dependent signaling is a primary mediator of the neuroendocrine, autonomic (fight-or-flight) and behavioral responses to stress, acting as a key regulator of adaptation by activating the hypothalamus-pituitary-adrenal axis, leading to corticotropin hormone (ACTH) production (By similarity). Mediates both anxiogenic and anxiolytic response to stress in glutamatergic and dopaminergic neurons, respectively (By similarity). CRHR1 also plays a critical role in addiction by mediating the brain's stress response, particularly during withdrawal and relapse: it drives the transition to compulsive drug seeking by increasing anxiety and negative emotional states (By similarity)..

Function from UniProtKB (P34998), read 2026-09-23. CC BY 4.0.