TY - JOUR
T1 - Nitric oxide-sensitive guanylyl cyclase is dispensable for nitrergic signaling and gut motility in mouse intestinal smooth muscle
AU - Groneberg, Dieter
AU - König, Peter
AU - Koesling, Doris
AU - Friebe, Andreas
N1 - Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2011/5
Y1 - 2011/5
N2 - Background & Aims: The nitric oxideguanosine 3',5'-cyclic monophosphate (cGMP) signaling pathway has an important role in the control of smooth muscle tone. NO is produced by NO synthases and acts as a major inhibitory neurotransmitter in the gastrointestinal (GI) tract. The main target, NO-sensitive guanylyl cyclase (NO-GC), is stimulated by NO to produce the intracellular messenger cGMP. We investigated the role of NO-GC in nitrergic relaxation and GI motility. Methods: We tested relaxation of GI smooth muscle in mice that do not express NO-GC or mice with disruption of NO-GC specifically in smooth muscle cells. Different segments of the GI tract (fundus, lower esophageal sphincter, pyloric sphincter, and duodenum) were used in isometric force studies. NO donors and electrical field stimulation were used to assess nitrergic signaling. Whole-gut transit time was measured as an indicator of GI motility. Results: Mice that lack NO-GC do not have NO-induced relaxation of GI smooth muscle. Gut transit time was increased, resulting in GI dysfunction. Surprisingly, in mice that lack NO-GC specifically in smooth muscle, NO-induced relaxation was reduced only slightly, and whole-gut transit time was unchanged compared with wild-type mice. Conclusions: Lack of NO-GC in smooth muscle cells does not impair NO-induced relaxation of GI tissues or GI motility. The NO receptor guanylyl cyclase in GI smooth muscle is therefore dispensable for nitrergic signaling in mice.
AB - Background & Aims: The nitric oxideguanosine 3',5'-cyclic monophosphate (cGMP) signaling pathway has an important role in the control of smooth muscle tone. NO is produced by NO synthases and acts as a major inhibitory neurotransmitter in the gastrointestinal (GI) tract. The main target, NO-sensitive guanylyl cyclase (NO-GC), is stimulated by NO to produce the intracellular messenger cGMP. We investigated the role of NO-GC in nitrergic relaxation and GI motility. Methods: We tested relaxation of GI smooth muscle in mice that do not express NO-GC or mice with disruption of NO-GC specifically in smooth muscle cells. Different segments of the GI tract (fundus, lower esophageal sphincter, pyloric sphincter, and duodenum) were used in isometric force studies. NO donors and electrical field stimulation were used to assess nitrergic signaling. Whole-gut transit time was measured as an indicator of GI motility. Results: Mice that lack NO-GC do not have NO-induced relaxation of GI smooth muscle. Gut transit time was increased, resulting in GI dysfunction. Surprisingly, in mice that lack NO-GC specifically in smooth muscle, NO-induced relaxation was reduced only slightly, and whole-gut transit time was unchanged compared with wild-type mice. Conclusions: Lack of NO-GC in smooth muscle cells does not impair NO-induced relaxation of GI tissues or GI motility. The NO receptor guanylyl cyclase in GI smooth muscle is therefore dispensable for nitrergic signaling in mice.
UR - http://www.scopus.com/inward/record.url?scp=79955473951&partnerID=8YFLogxK
U2 - 10.1053/j.gastro.2011.01.038
DO - 10.1053/j.gastro.2011.01.038
M3 - Journal articles
AN - SCOPUS:79955473951
SN - 0016-5085
VL - 140
SP - 1608
EP - 1617
JO - Gastroenterology
JF - Gastroenterology
IS - 5
ER -