Carbon monoxide, hydrogen sulfide, and nitric oxide as signaling molecules in the gastrointestinal tract

Gastroenterology. 2014 Aug;147(2):303-13. doi: 10.1053/j.gastro.2014.04.041. Epub 2014 May 2.


Carbon monoxide (CO) and hydrogen sulfide (H2S) used to be thought of simply as lethal and (for H2S) smelly gaseous molecules; now they are known to have important signaling functions in the gastrointestinal tract. CO and H2S, which are produced in the gastrointestinal tract by different enzymes, regulate smooth muscle membrane potential and tone, transmit signals from enteric nerves, and can regulate the immune system. The pathways that produce nitric oxide, H2S, and CO interact; each can inhibit and potentiate the level and activity of the other. However, there are significant differences between these molecules, such as in half-lives; CO is more stable and therefore able to have effects distal to the site of production, whereas nitric oxide and H2S are short lived and act only close to sites of production. We review their signaling functions in the luminal gastrointestinal tract and discuss how their pathways interact. We also describe other physiological functions of CO and H2S and how they might be used as therapeutic agents.

Keywords: Gases; Gastrointestinal Motility; Neurotransmission; Signal Transduction; Smooth Muscle.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Animals
  • Carbon Monoxide / metabolism*
  • Carbon Monoxide / therapeutic use
  • Enteric Nervous System / metabolism
  • Gastrointestinal Agents / therapeutic use
  • Gastrointestinal Tract / drug effects
  • Gastrointestinal Tract / immunology
  • Gastrointestinal Tract / innervation
  • Gastrointestinal Tract / metabolism*
  • Humans
  • Hydrogen Sulfide / metabolism*
  • Hydrogen Sulfide / therapeutic use
  • Muscle, Smooth / drug effects
  • Muscle, Smooth / immunology
  • Muscle, Smooth / innervation
  • Muscle, Smooth / metabolism*
  • Nitric Oxide / metabolism*
  • Signal Transduction* / drug effects


  • Gastrointestinal Agents
  • Nitric Oxide
  • Carbon Monoxide
  • Hydrogen Sulfide