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.