NO, CO and H₂S: A trinacrium of bioactive gases in the brain

Oxygen and carbon dioxide are time honored gases that have direct bearing on almost all life forms, but over the past thirty years, and in large part due to the Nobel Prize Award in Medicine for the elucidation of nitric oxide (NO) as a bioactive gas, the research and medical communities now recognize other gases as critical for survival. In addition to NO, hydrogen sulfide (H₂S) and carbon monoxide (CO) have emerged as a triumvirate or Trinacrium of gases with analogous importance and that serve important homeostatic functions. Perhaps, one of the most intriguing aspects of these gases is the functional interaction between them, which is intimately linked by the enzyme systems that produce them. Despite the need to better understand NO, H₂S and CO biology, the notion that these are environmental pollutants remains ever present. For this reason, incorporating the concept of hormesis becomes imperative and must be included in discussions when considering developing new therapeutics that involve these gases. While there is now an enormous literature base for each of these gasotransmitters, we provide here an overview of their respective physiologic roles in the brain.