AJP - Gastrointestinal and Liver Physiology, Vol 273, Issue 2 365-G373, Copyright © 1997 by American Physiological Society

ARTICLES

Protective action of gastrin-17 against alcohol-induced gastric injury in the rat: role in mucosal defense

D. W. Mercer, J. M. Cross, G. S. Smith and T. A. Miller
Department of Surgery, University of Texas, Houston Medical School 77030, USA.

Exogenous cholecystokinin (CCK) or exposure of the stomach to the mild irritant 25% ethanol can prevent gastric injury. Ingestion of ethanol also elicits the release of CCK as well as gastrin, which is structurally similar to CCK. This study was undertaken in conscious rats to examine the gastroprotective actions of gastrin and to assess the effect of CCK-gastrin receptor blockade on adaptive cytoprotection with ethanol as the mild irritant. Intravenous (1-25 pmol/kg) administration of gastrin-17 dose dependently increased gastric mucosal blood flow (laser Doppler) and reduced gastric injury caused by 1 ml of orally administered acidified ethanol (150 mM HCl-50% ethanol). Similar gastroprotection was achieved with the gastrin secretagogue 5% peptone (1 ml orogastrically). The gastroprotective capabilities of gastrin-17 were attenuated by the type B CCK (gastrin) receptor antagonist L-365,260 (12.5-25 mg/kg i.p.) and by capsaicin desensitization (125 mg/kg s.c.). CCK octapeptide (5 nmol/kg i.v.)-induced protection was reversed by the type A CCK receptor antagonist MK-329 (1 mg/kg i.p.). Neither receptor antagonist, alone or in combination, reversed the protective effects of the mild irritant 25% ethanol (1 ml orogastrically). Thus, whereas gastrin may play a role in gastric mucosal defense, neither CCK nor gastrin appears to participate in the phenomenon of adaptive cytoprotection.

This article has been cited by other articles:

				S. D. West, K. S. Helmer, L. K. Chang, Y. Cui, G. H. Greeley, and D. W. Mercer Cholecystokinin secretagogue-induced gastroprotection: role of nitric oxide and blood flow Am J Physiol Gastrointest Liver Physiol, March 1, 2003; 284(3): G399 - G410. [Abstract] [Full Text] [PDF]

				S. Tsuji, W.-H. Sun, M. Tsujii, N. Kawai, A. Kimura, Y. Kakiuchi, S. Yasumaru, M. Komori, H. Murata, Y. Sasaki, et al. Lansoprazole Induces Mucosal Protection through Gastrin Receptor-Dependent Up-Regulation of Cyclooxygenase-2 in Rats J. Pharmacol. Exp. Ther., December 1, 2002; 303(3): 1301 - 1308. [Abstract] [Full Text] [PDF]

				M. Komori, S. Tsuji, W.-H. Sun, M. Tsujii, N. Kawai, M. Yasumaru, Y. Kakiuchi, A. Kimura, Y. Sasaki, S. Higashiyama, et al. Gastrin enhances gastric mucosal integrity through cyclooxygenase-2 upregulation in rats Am J Physiol Gastrointest Liver Physiol, December 1, 2002; 283(6): G1368 - G1378. [Abstract] [Full Text] [PDF]

				M. K. Jones, R. M. Itani, H. Wang, M. Tomikawa, I. J. Sarfeh, S. Szabo, and A. S. Tarnawski Activation of VEGF and Ras genes in gastric mucosa during angiogenic response to ethanol injury Am J Physiol Gastrointest Liver Physiol, June 1, 1999; 276(6): G1345 - G1355. [Abstract] [Full Text] [PDF]

				D. W. Mercer, A. A. Castaneda, J. W. Denning, L. Chang, and D. H. Russell Effects of endotoxin on gastric injury from luminal irritants in rats: potential roles of nitric oxide Am J Physiol Gastrointest Liver Physiol, September 1, 1998; 275(3): G449 - G459. [Abstract] [Full Text] [PDF]