Gastrin enhances gastric mucosal integrity through cyclooxygenase-2 upregulation in rats

Gastrin, PGs, and growth factors have important roles in maintaining gastrointestinal mucosal integrity. Cyclooxygenases (COX-1 and COX-2) are the key enzymes involved in PG synthesis. This study aimed to clarify the mechanisms of gastric mucosal protection by gastrin. Fasted rats were administered...

Full description

Saved in:
Bibliographic Details
Published in:American journal of physiology: Gastrointestinal and liver physiology 2002-12, Vol.46 (6), p.G1368-G1378
Main Authors: KOMORI, Masato, TSUJI, Shingo, KAWANO, Sunao, HORI, Masatsugu, SUN, Wei-Hao, TSUJII, Masahiko, KAWAI, Naoki, YASUMARU, Masakazu, KAKIUCHI, Yoshimi, KIMURA, Arata, SASAKI, Yutaka, HIGASHIYAMA, Shigeki
Format: Article
Language:English
Subjects:
Anatomy & physiology
Biological and medical sciences
Body fluids
Digestive system
Fundamental and applied biological sciences. Psychology
Rodents
Stomach
Vertebrates: digestive system
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary:Gastrin, PGs, and growth factors have important roles in maintaining gastrointestinal mucosal integrity. Cyclooxygenases (COX-1 and COX-2) are the key enzymes involved in PG synthesis. This study aimed to clarify the mechanisms of gastric mucosal protection by gastrin. Fasted rats were administered subcutaneous gastrin 17 with or without gastrin receptor antagonist YM022 pretreatment. Heparin-binding epidermal growth factor-like growth factor (HB-EGF) and COX-2 expression were examined using Western blot analysis. Another series of experiments investigated 1) PGE2 levels in gastric mucosa, 2) the protective action of gastrin against gastric damage by acidified ethanol, 3) the effects of a specific HB-EGF-neutralizing antibody on gastrin-induced COX-2 expression, and 4) the effects of a specific COX-2 inhibitor NS-398 on PGE2 synthesis and the mucosal protection afforded by gastrin. Gastrin dose-dependently increased HB-EGF, COX-2 expression, and PGE2 levels and reduced gastric damage. However, pretreatment with YM022 dose-dependently abolished such effects of gastrin. A specific HB-EGF- neutralizing antibody and an EGF receptor inhibitor decreased gastrin-induced COX-2 expression. NS-398 blocked gastrin-induced PGE2 synthesis and mucosal protection. In conclusion, this study demonstrates that gastrin enhances gastric mucosal integrity through COX-2, which is partially mediated by HB-EGF, and PGE2 upregulation in rats.
ISSN:0193-1857
1522-1547