{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:03:10Z","timestamp":1791295390102,"version":"4.1.0"},"reference-count":50,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2013,3,28]],"date-time":"2013-03-28T00:00:00Z","timestamp":1364428800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Neurogastroenterology Motil"],"published-print":{"date-parts":[[2013,5]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Soluble guanylate cyclase (<jats:styled-content style=\"fixed-case\">sGC<\/jats:styled-content>) is the principal target of nitric oxide (NO) to control gastrointestinal motility. The consequence on nitrergic signaling and gut motility of inducing a heme\u2010free status of<jats:styled-content style=\"fixed-case\">sGC<\/jats:styled-content>, as induced by oxidative stress, was investigated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>sGC\u03b2<jats:sub>1<\/jats:sub><jats:sup>H105F<\/jats:sup>knock\u2010in (apo\u2010sGC) mice, which express heme\u2010free sGC that has basal activity, but cannot be stimulated by NO, were generated.<\/jats:p><\/jats:sec><jats:sec><jats:title>Key Results<\/jats:title><jats:p>Diethylenetriamine NONOate did not increase<jats:styled-content style=\"fixed-case\">sGC<\/jats:styled-content>activity in gastrointestinal tissue of apo\u2010<jats:styled-content style=\"fixed-case\">sGC<\/jats:styled-content>mice. Exogenous NO did not induce relaxation in fundic, jejunal and colonic strips, and pyloric rings of apo\u2010<jats:styled-content style=\"fixed-case\">sGC<\/jats:styled-content>mice. The stomach was enlarged in apo\u2010<jats:styled-content style=\"fixed-case\">sGC<\/jats:styled-content>mice with hypertrophy of the muscularis externa of the fundus and pylorus. In addition, gastric emptying and intestinal transit were delayed and whole\u2010gut transit time was increased in the apo\u2010<jats:styled-content style=\"fixed-case\">sGC<\/jats:styled-content>mice, while distal colonic transit time was maintained. The nitrergic relaxant responses to electrical field stimulation at 1\u20134\u00a0Hz were abolished in fundic and jejunal strips from apo\u2010<jats:styled-content style=\"fixed-case\">sGC<\/jats:styled-content>mice, but in pyloric rings and colonic strips, only the response at 1\u00a0Hz was abolished, indicating the contribution of other transmitters than NO.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions &amp; Inferences<\/jats:title><jats:p>The results indicate that the gastrointestinal consequences of switching from a native<jats:styled-content style=\"fixed-case\">sGC<\/jats:styled-content>to a heme\u2010free<jats:styled-content style=\"fixed-case\">sGC<\/jats:styled-content>, which cannot be stimulated by NO, are most pronounced at the level of the stomach establishing a pivotal role of the activation of<jats:styled-content style=\"fixed-case\">sGC<\/jats:styled-content>by NO in normal gastric functioning. In addition, delayed intestinal transit was observed, indicating that nitrergic activation of<jats:styled-content style=\"fixed-case\">sGC<\/jats:styled-content>also plays a role in the lower gastrointestinal tract.<\/jats:p><\/jats:sec>","DOI":"10.1111\/nmo.12120","type":"journal-article","created":{"date-parts":[[2013,3,28]],"date-time":"2013-03-28T13:39:44Z","timestamp":1364477984000},"source":"Crossref","is-referenced-by-count":14,"title":["Heme deficiency of soluble guanylate cyclase induces gastroparesis"],"prefix":"10.1111","volume":"25","author":[{"given":"S. M. 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