Regulation of Colonic Ion Transport by Gasotransmitters

Gaseous molecules such as nitric oxide (NO), hydrogen sulfide (H2S), or carbon monoxide (CO) are involved in the regulation of colonic water and salt transport, which can be switched between absorption and secretion. Nitric oxide is produced from the amino acid L-arginine by different isoforms of the enzyme NO synthase, which are expressed both by enteric neurones and by the colonic epithelium. NO donors evoke a transepithelial Cl- secretion in vitro. Most actions of NO are mediated by a stimulation of guanosine 5' cyclic monophosphate (cGMP) synthesis via activation of the soluble guanylate cyclase. In rat colon, NO possesses several main action sites: a stimulation of apical Cl- channels most probably not related to cGMP-dependent phosphorylation, and an increase in the cytosolic Ca2+ concentration, which stimulates a Ca2+-dependent K+ conductance in the basolateral membrane. Hydrogen sulfide, produced during the metabolism of the amino acid L-cysteine, also evokes a Cl- secretion, either by stimulation of secretomotor submucosal neurones as in guinea-pig colon or by activating Ca2+-dependent and ATP-sensitive K+ channels as in rat colon. The third gasotransmitter, CO, produced during the degradation of heme, evokes anion secretion carried by Cl- and HCO3-. This response is mainly caused by the activation of apical anion channels and a stimulation of Ca2+-dependent K+ channels via an increase of the cytosolic Ca2+ concentration. Consequently, gaseous molecules produced by enteric neurones, epithelial cells, as well-in the case of H2S-the microbial flora affect key transport enzymes involved in colonic ion transport.