Small intestinal motility in soluble guanylate cyclase alpha1 knockout mice: (Jejunal phenotyping of sGCalpha1 knockout mice).

Nitric oxide (NO) activates soluble guanylate cyclase (sGC) to produce guanosine-3',5'-cyclic-monophosphate (cGMP). The aim of this study was to investigate the nitrergic regulation of jejunal motility in sGCalpha(1) knockout (KO) mice. Functional responses to nitrergic stimuli and cGMP levels in response to nitrergic stimuli were determined in circular muscle strips. Intestinal transit was determined. Nitrergic relaxations induced by electrical field stimulation and exogenous NO were almost abolished in male KO strips, but only minimally reduced and sensitive to ODQ in female KO strips. Basal cGMP levels were decreased in KO strips, but NO still induced an increase in cGMP levels. Transit was not attenuated in male nor female KO mice. In vitro, sGCalpha(1)beta(1) is the most important isoform in nitrergic relaxation of jejunum, but nitrergic relaxation can also occur via sGCalpha(2)beta(1) activation. The latter mechanism is more pronounced in female than in male KO mice. In vivo, no important implications on intestinal motility were observed in male and female KO mice.