Gaseous compounds such as NO, CO or H₂S are more and more considered to act as 'gasotransmitters' regulating the function of different organs. H₂S is produced by enteric neurons, which express the two key enzymes for H₂S production, cystathionin-b-synthase (CBS) und cystathionin-g-lyase (CSE) suggesting a role of this compound in the regulation of gastrointestinal functions such as ion transport. In the present study we investigated the action of an H₂S donor, NaHS, on transepithelial ion transport across rat distal colon.

NaHS induced a triphasic change in short-circuit current (Isc): an initial, short-lasting increase, a secondary fall, and a tertiary long-lasting increase in Isc. Experiments with blockers of Cl^- secretion such as bumetanide, an inhibitor of the basolateral Na⁺-K⁺-2Cl^--cotransporter, or mucosal glibenclamide, a blocker of the apical CFTR Cl^- channel, as well as anion substitution experiments indicated that both phases of the Isc increase induced by H₂S are due to Cl^- secretion. In contrast, the sensitivity against mucosal tetrapentylammonium suggests that a K⁺ secretion contributes to the negative Isc induced during the 2. phase of the H₂S response. Tissues responded to lower concentrations of NaHS after blockade of CSE, suggesting that a spontaneous production of H₂S causes a desensitization to the exogenous H₂S donor.

Experiments, in which epithelia were apically permeabilized with the ionophore nystatin, revealed a stimulation of basolateral K⁺ currents by NaHS as one of the main mechanisms for activation of transepithelial anion secretion. Concomitantly, an increase in the cytosolic Ca²⁺ concentration was observed at isolated crypts from rat colon.

In further experiments, it shall be clarified, which role Ca²⁺-dependent and/or ATP-sensitive K⁺ channels play in the response to this gasotransmitter.