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Ecabet sodium induces neuronal nitric oxide synthase-derived nitric oxide synthesis and gastric adaptive relaxation in the human stomach

  • Original Article—Alimentary Tract
  • Published:
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Abstract

Background

Gastric adaptive relaxation (GAR) is a major factor of functional dyspepsia (FD). Nitric oxide (NO) could be the key molecule responsible for GAR. We previously reported that the physiological gastric reservoir ability can be evaluated by measuring the cross-sectional area of the proximal stomach by abdominal ultrasonography (US). Ecabet sodium (ES), a gastro-protective antiulcer agent, has been shown to improve symptoms in FD patients. We examined the effects of ES on GAR in humans and on NO synthesis in vitro.

Methods

GAR was measured by US in 14 subjects, 8 of whom had a pressure sensor inserted into their stomach, after treatment with ES, placebo, or no drugs. NO was measured in SH-SY 5Y cells using a fluorescent indicator. Neuronal, endothelial and inducible NO synthase (nNOS, eNOS and iNOS, respectively) expressions were examined in SH-SY 5Y cells by Western blotting.

Results

Compared to placebo, ES induced significantly greater dilatation of the proximal stomach after the subjects drank 300–400 ml water (P < 0.05). After ES intake, the intragastric pressure did not change significantly, but it tended to be lower (n = 8; P = 0.15). ES increased NO production and nNOS expression, but not iNOS or eNOS expression, in SH-SY 5Y cells in vitro. Pretreatment with non-selective NO synthase (NOS) inhibitor, but not with iNOS-selective inhibitor, reduced NO production by ES.

Conclusion

ES may promote GAR in humans through nNOS-related NO; therefore, it may be useful for patients with FD.

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Abbreviations

ANOVA:

Analysis of variance

CGRP:

Calcitonin gene-related peptide

CPSN:

Capsaicin-sensitive afferent nerves

DAF-2:

Diaminofluorescein-2

ES:

Ecabet sodium

FD:

Functional dyspepsia

GAR:

Gastric adaptive relaxation

NO:

Nitric oxide

NOS:

Nitric oxide synthase

nNOS:

Neuronal nitric oxide synthase

eNOS:

Endothelial nitric oxide synthase

iNOS:

Inducible nitric oxide synthase

US:

Ultrasonography

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Acknowledgments

We thank Professor Masaharu Yoshihara (Health Service Center of Hiroshima University) and Professor Yukihito Higashi (Department of Cardiovascular Physiology and Medicine, Hiroshima University) for their valuable suggestions. This study was carried out at the Analysis Center of Life Science, Hiroshima University.

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Authors and Affiliations

  1. Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University, 1-2-3 Kasumi, Minami-ku, Hiroshima, 734-8551, Japan

    Yoshiaki Matsumoto, Masanori Ito, Masataka Tsuge, Taiji Matsuo & Kazuaki Chayama

  2. Department of Endoscopy, Hiroshima University Hospital, Hiroshima, Japan

    Shinji Tanaka

  3. Department of Gastroenterology, Kawasaki Medical School, Kurashiki, Japan

    Ken Haruma

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  1. Yoshiaki Matsumoto
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  2. Masanori Ito
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Correspondence to Masanori Ito.

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Matsumoto, Y., Ito, M., Tsuge, M. et al. Ecabet sodium induces neuronal nitric oxide synthase-derived nitric oxide synthesis and gastric adaptive relaxation in the human stomach. J Gastroenterol 44, 1118–1124 (2009). https://doi.org/10.1007/s00535-009-0113-z

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  • DOI: https://doi.org/10.1007/s00535-009-0113-z

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