Role of nitric oxide on physiological regulation and pathophysiology of gastric acid
Grant-in-Aid for Scientific Research (C)
|Allocation Type||Single-year Grants|
|Research Institution||Hiroshima University|
SUMII Koji Hiroshima University, Faculty of Medicine, Associate Professor, 医学部, 助教授 (00116609)
SUMII Masaharu Hiroshima Uniiversity, Research Institution for Radiation Biologu and Medicine, Assistant Professor, 原爆放射能医学研究所, 講師 (60284220)
|Project Period (FY)
1998 – 2000
Completed(Fiscal Year 2000)
|Budget Amount *help
¥3,200,000 (Direct Cost : ¥3,200,000)
Fiscal Year 2000 : ¥900,000 (Direct Cost : ¥900,000)
Fiscal Year 1999 : ¥800,000 (Direct Cost : ¥800,000)
Fiscal Year 1998 : ¥1,500,000 (Direct Cost : ¥1,500,000)
|Keywords||nitric oxide / iNOS / nitrite / LPS / gastric acid / gastrin / somatostatin / gastric cancer / Lipopolysaccharide / NO / ソマトスタチン / 胃酸 / 血清NOX / pepsinogen / 胃液nitrite / 胃癌 / H+K+ATPase / 胃酸分泌 / lipopolysaccharide / ガストリン / 胃液 / 一酸化窒素(NO) / カプサイシン / 知覚神経|
Recent studies of the H.pylori-induced gastritis suggest that the inflammatory process affect on gastric secretion. In this study we have clarified the role of nitric oxide on the regulation of gastric endocrine and exocrine secretion, and relevance to gastric diseases.
1. The role of capsaicin-sensitive afferenr neuron on pH dependent gastrin secretion.
We indicated that capsaicin-sensitive afferent neurons participate in the secretion of gastrin by luminal alkalization and inhibition by acidification. NO was also considered to be one of candidate that regulate pH-dependant gastrin secretion because serum levels of NOX were affected by the change of luminal pH.But further studies were needed to clarify the precise relationship among capsaicin-senseitive neuron, NO and G cells.
2. Regulation of gastric secretion by nitric oxide
Bacterial lipopolysaccharide (LPS) exert on inflammatory cells to produce NO.Low doses of LPS (100μg/kg) inhibited the gastric acid secretion, while it did not alte
r serum levels of NOX.LPS increased iNOS activity, iNOS mRNA, somatostatin mRNA, and decrease of gastrin mRNA and HK-ATPase mRNA.These changes were reversed by L-NAME.The results indicated that the LPS-induced NO inhibited gastric acid secretion via the stimulation of somatostatin secretion and synthesis.
3. Serum NOX as the marker of gastric inflammation and secretion
In this study we demonstrated that serum NOX levels were significantly increased in H.pylori-positive subjects than that of H.pylori-negative. In H.pylori-induced gastritis the serum NOX levels increase before the increase of serum pepsinogen levels, and in H.pylori-negative subjects serum NOX levels correlate serum PGI and PGII.These results suggest that NOX can be used as a marker of gastric mucosal inflammation and acid secretion.
4. Nitrite in gastric juice and gastric cancer
N-nitrosocompounds, carcinogen in gastric juice, were produced from nitrite. The high pH of gastric juice is one of major determinant of the nitrite in gastric juice. Hypochlorhydria is responsible for increased nitrite levels both in patients with gastric cancer and atrophic gastritis, but in patients with gastric cancer additional factors affect on the formation of intraluminal N-nitrosocompounds and their precursors because gastric juice nitrite levels were significantly higher in patients with gastric cancer than those in atrophic gastritis in spite of same pH. Less
Research Output (28results)