title: Review article: carbon monoxide in gastrointestinal physiology and its potential in therapeutics.
abstract: BACKGROUND
  While carbon monoxide (CO) is a known toxin, it is now recognised that CO is also an important signalling molecule involved in physiology and pathophysiology.
  
  
  OBJECTIVE
  To summarise our current understanding of the role of endogenous CO in the regulation of gastrointestinal physiology and pathophysiology, and to potential therapeutic applications of modulating CO.
  
  
  METHODS
  This review is based on a comprehensive search of the Ovid Medline comprehensive database and supplemented by our ongoing studies evaluating the role of CO in gastrointestinal physiology and pathophysiology.
  
  
  RESULTS
  Carbon monoxide derived from haem oxygenase (HO)-2 is predominantly involved in neuromodulation and in setting the smooth muscle membrane potential, while CO derived from HO-1 has anti-inflammatory and antioxidative properties, which protect gastrointestinal smooth muscle from damage caused by injury or inflammation. Exogenous CO is being explored as a therapeutic agent in a variety of gastrointestinal disorders, including diabetic gastroparesis, post-operative ileus, organ transplantation, inflammatory bowel disease and sepsis. However, identifying the appropriate mechanism for safely delivering CO in humans is a major challenge.
  
  
  CONCLUSIONS
  Carbon monoxide is an important regulator of gastrointestinal function and protects the gastrointestinal tract against noxious injury. CO is a promising therapeutic target in conditions associated with gastrointestinal injury and inflammation. Elucidating the mechanisms by which CO works and developing safe CO delivery mechanisms are necessary to refine therapeutic strategies.
authors.affiliation: Enteric NeuroScience Program, Mayo Clinic, Rochester, MN 55905, USA.
authors.forename: S J
authors.initials: SJ
authors.lastname: Gibbons
authors.forename: P-J
authors.initials: PJ
authors.lastname: Verhulst
authors.forename: A
authors.initials: A
authors.lastname: Bharucha
authors.forename: G
authors.initials: G
authors.lastname: Farrugia
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000627:therapeutic use; D002248:Carbon Monoxide / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D005767:Gastrointestinal Diseases / Q000188:drug therapy* / Q000503:physiopathology; D041981:Gastrointestinal Tract / Q000502:physiology* / Q000503:physiopathology; D006419:Heme Oxygenase (Decyclizing) / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000188:drug therapy; D009130:Muscle, Smooth / Q000378:metabolism; D018805:Sepsis / Q000188:drug therapy
chemical_list: D000893:Anti-Inflammatory Agents; D002248:Carbon Monoxide; D006419:Heme Oxygenase (Decyclizing); D051547:Heme Oxygenase-1; C105245:heme oxygenase-2