The physiological and pharmacological relevance of soluble guanylate cyclase (sGC) in the gastro-intestinal tract.

A first research area deals with the physiological and pharmacological relevance of soluble guanylate cyclase (sGC) in the gastro-intestinal tract.

sGC is a heterodimer consisting of an α and a β subunit. Both subunits have 2 isoforms : α1 and α2, β1 and β2. The 2 physiological relevant dimers are α1β1 and α2β. In the gastro-intestinal tract, mainly α1β1 is present. sGC is the most important target of NO in the gastro-intestinal tract although also other targets have been described.

The relative importance of sGCα1β1, versus sGCα2β1, and the role of sGC in the effect of NO on gastro-intestinal motility is investigated in vitro and in vivo (gastric emptying, intestinal transit) by use of sGCα1 knockout and sGCβ1 mutant mice. The influence of sGC stimulators and sGC activators such as cinaciguat on gastro-intestinal motility is studied.