Gastrointestinal Physiology - Gianrico Farrugia

Small Gaseous Signaling Molecules

In addition to nitric oxide, a well-characterized molecule, there are two other molecules that exist as gases at normal atmospheric pressure and temperature and have roles in gastrointestinal physiology.

Carbon monoxide

Carbon monoxide is a gas that is physiologically produced in most species, including humans. The major route of production of carbon monoxide is through the breakdown of heme by heme oxygenase. Two isoforms of heme oxygenase have been fully characterized.

Work in Dr. Farrugia's laboratory has described activation of a delayed rectifier potassium channel by carbon monoxide and the presence of heme oxygenase in a subset of enteric neurons and in mouse interstitial cells of Cajal. Recent work on knockout mice lacking heme oxygenase-2 has revealed a role for carbon monoxide as a novel neuromodulator in the gastrointestinal tract.

The cytoprotective role of carbon monoxide derived from heme oxygenase-1 has also been a focus of the lab's studies on diabetic gastroparesis.

Hydrogen sulfide

Though it is not controversial to state that hydrogen sulfide is present in the gastrointestinal tract, the physiological roles for this gaseous molecule have only recently been identified. The lab has investigated the effects of hydrogen sulfide on voltage-gated Na+ channels in an effort to understand physiological targets for endogenously produced hydrogen sulfide.