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


CONCLUSIONS
ES may promote GAR in humans through nNOS-related NO; therefore, it may be useful for patients with FD.
Matsumoto
Yoshiaki
Y
Department of Medicine and Molecular Science, Graduate School of Biomedical Sciences, Hiroshima University, Minami-ku, Hiroshima, Japan.
Ito
Masanori
M
Tsuge
Masataka
M
Matsuo
Taiji
T
Tanaka
Shinji
S
Haruma
Ken
K
Chayama
Kazuaki
K
D045784:Abietanes / Q000494:pharmacology*; D000328:Adult; D000897:Anti-Ulcer Agents / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004415:Dyspepsia / Q000188:drug therapy / Q000503:physiopathology; D013271:Gastric Dilatation / Q000139:chemically induced; D005753:Gastric Mucosa / Q000378:metabolism; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008297:Male; D009569:Nitric Oxide / Q000096:biosynthesis*; D052248:Nitric Oxide Synthase Type I / Q000187:drug effects* / Q000235:genetics; D052247:Nitric Oxide Synthase Type II / Q000187:drug effects / Q000235:genetics; D052250:Nitric Oxide Synthase Type III / Q000187:drug effects / Q000235:genetics; D011312:Pressure; D013270:Stomach / Q000000981:diagnostic imaging / Q000187:drug effects; D014463:Ultrasonography
D045784:Abietanes; D000897:Anti-Ulcer Agents; C061681:ecabet; D009569:Nitric Oxide; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D052250:Nitric Oxide Synthase Type III
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