Role of corticotropin-releasing factor in stress-related visceral hyperalgesia.

摘要

Corticotropin-releasing factor (CRF, also known as corticotropin-releasing hormone) was characterized in 1981 as a novel 41-amino-acid hypothalamic peptide that stimulates the synthesis and release of adrenocorticotropichormone (ACTH) and beta-endorphin from the pituitary. Activation of CRF pathways in the brain has been shown to reproduce the overall endocrine, autonomic, visceral, and behavioral response to stress. Recently, the CRF family has been expanded by the addition of three novel mammalian CRF-related peptides, urocortin 1 (also known as urocortin), urocortin 2 (also known as stresscopin-related peptide), and urocortin 3 (also known as stresscopin). CRF ligands interact with CRF receptor subtype 1 (CRF_1) and/or subtype 2 (CRF_2), cloned from two distinct genes. Several CRF_1 receptor splice variants, producing at least eight isoforms, and three functional isoforms of CRF_2 receptors have been identified in humans. One of the important characteristics of CRF receptor subtypes is their distinct affinity for mammalian CRF family ligands. CRF has higher affinity (10- to 40-fold) for CRF_1 than for CRF_2 receptor. In contrast, both urocortin 2 and 3 exhibit high selectivity for CRF_2 receptor.