Volume 145, Issue 1, Pages 188-196 (July 2013) Cell-Specific Deletion of Nitric Oxide–Sensitive Guanylyl Cyclase Reveals a Dual Pathway for Nitrergic Neuromuscular Transmission in the Murine Fundus  Dieter Groneberg, Barbara Lies, Peter König, Ronald Jäger, Barbara Seidler, Sabine Klein, Dieter Saur, Andreas Friebe  Gastroenterology  Volume 145, Issue 1, Pages 188-196 (July 2013) DOI: 10.1053/j.gastro.2013.03.042 Copyright © 2013 AGA Institute Terms and Conditions

Figure 1 NO-induced fundus relaxation. Fundus strips from SM-GCKO (A), ICC-GCKO (B), and SM/ICC-GCKO (C) and respective controls were precontracted with 0.1 μmol/L CCh. To compare the effect of higher precontraction, fundus from SM-GCKO (D) and ICC-GCKO (E) were also precontracted with 10 μmol/L CCh. Relaxation was induced by the addition of increasing concentrations of the NO donor DEA-NO. Data shown are mean ± SEM of N = 5−12 per genotype. A model for nitrergic relaxation in the fundus is shown in (F). Gastroenterology 2013 145, 188-196DOI: (10.1053/j.gastro.2013.03.042) Copyright © 2013 AGA Institute Terms and Conditions

Figure 2 Lack of ICC-mediated fundus relaxation in the presence of nifedipine. Fundus strips from SM-GCKO (A) and ICC-GCKO (B) and respective controls were precontracted with 0.1 μmol/L CCh in the presence of 1 μmol/L nifedipine and then relaxed by the addition of the NO-donor DEA-NO. Addition of the Rho kinase blocker Y27632 fully relaxed fundus strips contracted with CCh in the presence of nifedipine indicating calcium-independent contraction. Interpretations of the data according to our model are shown in the insets. Data shown are mean ± SEM of N = 4−6 per genotype. Gastroenterology 2013 145, 188-196DOI: (10.1053/j.gastro.2013.03.042) Copyright © 2013 AGA Institute Terms and Conditions

Figure 3 EFS-induced fundus relaxation under NANC conditions. Fundus strips from control (A) SM-GCKO (B), ICC-GCKO (C), and SM/ICC-GCKO (D) were precontracted with 0.1 μmol/L U46619 in the presence of 1 μmol/L atropine and 1 μmol/L guanethidine. Relaxation by endogenous NO was provoked by the stimulation with an electrical field in the absence or presence of the NO-GC stimulator Bay 41-2272. Data shown are mean ± SEM of N = 4−6 per genotype. Gastroenterology 2013 145, 188-196DOI: (10.1053/j.gastro.2013.03.042) Copyright © 2013 AGA Institute Terms and Conditions

Figure 4 EFS-induced responses in the absence of precontraction and NANC conditions. Fundus strips from control, SM-GCKO, ICC-GCKO, and SM/ICC-GCKO were mounted into the organ bath without precontraction. Atropine and guanethidine were also omitted. Fundus strips were stimulated by applying an electric field with increasing frequency. EFS was then repeated after the addition of 10 μM ODQ. Original traces for control and SM/ICC-GCKO are shown in (A), the statistical analysis of the inhibition of 4-Hz contraction for control and all knockout animals is shown in (B). Data shown are mean ± SEM of N = 5−11 per genotype. Gastroenterology 2013 145, 188-196DOI: (10.1053/j.gastro.2013.03.042) Copyright © 2013 AGA Institute Terms and Conditions

Figure 5 Increased gut motility in SM/ICC-GCKO mice. Whole gut transit time was measured by the application of carmine into the stomach. Each symbol represents the transit time of one animal tested. The bars represent mean values. Data shown are N = 18−32 per genotype. Gastroenterology 2013 145, 188-196DOI: (10.1053/j.gastro.2013.03.042) Copyright © 2013 AGA Institute Terms and Conditions