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

David W. Mercer, James M. Cross, Gregory S. Smith, Thomas A. Miller

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

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 ip) and by capsaicin desensitization (125 mg/kg sc). CCK octapeptide (5 nmol/kg iv)-induced protection was reversed by the type A CCK receptor antagonist MK-329 (1 mg/kg ip). 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.

Original languageEnglish (US)
Pages (from-to)G365-G373
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume273
Issue number2 36-2
DOIs
StatePublished - 1997
Externally publishedYes

Keywords

  • Adaptive cytoprotection
  • Capsaicin
  • Cholecystokinin
  • Cholecystokinin receptors
  • Mild irritants

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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