| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Articles in PresS, published online ahead of print August 14, 2002
Am J Physiol Gastrointest Liver Physiol, 10.1152/ajpgi.00006.2002
Submitted on January 7, 2002
Accepted on July 30, 2002
1 Department of Internal Medicine and Therapeutics, Osaka University Graduate School of Medicine, Osaka, 565-0871, Japan
2 Department of Biochemistry, Osaka University Graduate School of Medicine, Osaka, 565-0871, Japan; Department of Clinical Laboratory Science, School of Allied Health Sciences, Osaka University Faculty of Medicine, Osaka, 565-0871, Japan
3 Department of Clinical Laboratory Science, School of Allied Health Sciences, Osaka University Faculty of Medicine, Osaka, 565-0871, Japan
* To whom correspondence should be addressed. E-mail: tsuji{at}medone.med.osaka-u.ac.jp.
Gastrin, prostaglandins (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.
This article has been cited by other articles:
|
|
 |
|
  S. Almeida-Vega, K. Catlow, S. Kenny, R. Dimaline, and A. Varro Gastrin activates paracrine networks leading to induction of PAI-2 via MAZ and ASC-1 Am J Physiol Gastrointest Liver Physiol, February 1, 2009; 296(2): G414 - G423. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Dimaline and A. Varro Attack and defence in the gastric epithelium - a delicate balance Exp Physiol, July 1, 2007; 92(4): 591 - 601. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. H. Dickson, A. Grabowska, M. El-Zaatari, J. Atherton, and S. A. Watson Helicobacter pylori Can Induce Heparin-Binding Epidermal Growth Factor Expression via Gastrin and Its Receptor. Cancer Res., August 1, 2006; 66(15): 7524 - 7531. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Kanda, H. Seno, M. Kawada, T. Sawabu, Y. Uenoyoma, T. Nakajima, Y. Konda, H. Fukui, T. Takeuchi, and T. Chiba Involvement of cyclooxygenase-2 in gastric mucosal hypertrophy in gastrin transgenic mice Am J Physiol Gastrointest Liver Physiol, March 1, 2006; 290(3): G519 - G527. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H K Baumgartner, O T Starodub, J S Joehl, L Tackett, and M H Montrose Cyclooxygenase 1 is required for pH control at the mouse gastric surface Gut, December 1, 2004; 53(12): 1751 - 1757. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH |
| Visit Other APS Journals Online |
