by Y Tache, et al.
July 31, 2009
[Note: corticotrophin-releasing factor (CRF) is a hormone and neurotransmitter involved in the stress response. A CRF receptor antagonist – proposed here as a possible therapy for IBS symptoms – would block or dampen CRF’s effects.]
Functional gastrointestinal disorders, which include irritable bowel syndrome (IBS), encompass a heterogeneous group of diseases identified by chronic or recurrent symptom-based diagnostic criteria.
Psychosocial factors are key components in the outcome of clinical manifestations of IBS symptoms. Anxiogenic and endocrine responses to stress are mediated by the corticotropin-releasing factor (CRF)-CRF1 receptor pathway.
Preclinical studies show that activation of the CRF1 receptor by exogenous CRF or stress recapitulates many functional symptoms of IBS diarrhea-predominant patients as related to:
• Anxiogenic/hypervigilant behavior,
• Autonomic nervous system alterations,
• Induction of diarrhea,
• Visceral hyperalgesia,
• Enhanced colonic motility,
• Mucus secretion,
• Increased permeability,
• Bacterial translocation,
• And mast cell activation,
…which are all alleviated by selective CRF1 receptor antagonists.
Clinical studies also support that CRF administration can induce IBS-like symptoms in healthy subjects and heighten colonic sensitivity in IBS patients. Yet to be ascertained is whether CRF1 receptor antagonists hold promise as a new therapy in IBS treatment.
Source: Current Gastroenterology Reports, Aug 2009;11(4):270-7. PMID: 19615302, by Taché Y, Kiank C, Stengel A. Center for Ulcer Research and Education-CURE: Digestive Diseases Research Center, VA Greater Los Angeles Healthcare System, Los Angeles, California, USA. [E-mail: ytache@mednet.ucla.edu]
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