title: Nitric oxide-sensitive guanylyl cyclase is dispensable for nitrergic signaling and gut motility in mouse intestinal smooth muscle.
abstract: OBJECTIVE
  The nitric oxide-guanosine 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.
authors.affiliation: Physiologisches Institut, Julius-Maximilians-Universität Würzburg, Würzburg, Germany.
authors.forename: Dieter
authors.initials: D
authors.lastname: Groneberg
authors.forename: Peter
authors.initials: P
authors.lastname: König
authors.forename: Doris
authors.initials: D
authors.lastname: Koesling
authors.forename: Andreas
authors.initials: A
authors.lastname: Friebe
mesh_terms: D000818:Animals; D017869:Cyclic GMP-Dependent Protein Kinases / Q000187:drug effects / Q000378:metabolism*; D005769:Gastrointestinal Motility / Q000187:drug effects / Q000502:physiology*; D006162:Guanylate Cyclase / Q000187:drug effects / Q000378:metabolism*; D007150:Immunohistochemistry; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects; D051379:Mice; D018345:Mice, Knockout; D009126:Muscle Relaxation / Q000187:drug effects / Q000502:physiology*; D032389:Myocytes, Smooth Muscle / Q000187:drug effects / Q000378:metabolism*; D009569:Nitric Oxide / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D009569:Nitric Oxide; D017869:Cyclic GMP-Dependent Protein Kinases; D006162:Guanylate Cyclase