Gastrin Enhances Gastric Mucosal Integrity Through Cyclooxygenase-2 Upregulation in Rats.
|
Accession number;03A0250898
|
| Title;Gastrin Enhances Gastric Mucosal Integrity Through Cyclooxygenase-2 Upregulation in Rats. |
| Author;
KOMORI MASATO
(Osaka Univ., Med. Sch.)
TSUJI SHINGO
(Osaka Univ., Med. Sch.)
TSUJII MASAHIKO
(Osaka Univ., Med. Sch.)
KAWANO SUNAO
(Osaka Univ., Med. Sch.)
|
Journal Title;Prog Med
|
Journal Code:F0664B
|
ISSN:0287-3648
|
|
VOL.23;NO.3;PAGE.814-818(2003)
|
| Figure&Table&Reference;FIG.3, REF.14 |
| Pub. Country;Japan |
| Language;Japanese |
| Abstract;Gastrin, prostaglandins (PGs) and growth factors have important roles in maintaining gastroin-testinal 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. (author abst.) |
|
|
|
Related Articles;
|
|
