Journal
STRESS, NEUROTRANSMITTERS, AND HORMONES: NEUROENDOCRINE AND GENETIC MECHANISMS
Volume 1148, Issue -, Pages 29-41Publisher
WILEY-BLACKWELL
DOI: 10.1196/annals.1410.007
Keywords
CRF; CRF receptors; CRF antagonists; colonic motor function; irritable bowel syndrome; stress
Funding
- National Institute of Arthritis, Metabolism and Digestive Diseases [R01 DK-33061, R01 DK-57236, DK-41301, P50 AR-049550]
- VA Merit and Senior Scientist Awards
- University of Wuerzburg/Germany
- European Academy of Science and Arts
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK033061, P30DK041301, R01DK057236, R01DK049550] Funding Source: NIH RePORTER
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Selye pioneered the concept of biological stress in 1936, culminating in the identification of the corticotropin-releasing factor (CRF) signaling pathways by Vale's group in the last two decades. The characterization of the 41 amino-acid CRF and other peptide members of the mammalian CRF family, urocortin 1, urocortin 2, and urocortin 3, and the cloning of CRF1 and CRF2 receptors, which display distinct affinity for CRF ligands, combined with the development of selective CRF receptor antagonists enable us to unravel the importance of CRF1 receptor in the stress-related endocrine (activation of pituitary-adrenal axis), behavioral (anxiety/depression, altered feeding), autonomic (activation of sympathetic nervous system), and immune responses. The activation of CRF1 receptors is also one of the key mechanisms through which various stressors impact the gut to stimulate colonic propulsive motor function and to induce hypersensitivity to colorectal distension as shown by the efficacy of the CRF1 receptor antagonists in blunting these stress-related components. The importance of CRF1 signaling pathway in the visceral response to stress in experimental animals provided new therapeutic approaches for treatment of functional bowel disorder such as irritable bowel syndrome, a multifactor functional disorder characterized by altered bowel habits and visceral pain, for which stress has been implicated in the pathophysiology and is associated with anxiety-depression in a subset of patients.
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