Cholecystokinin is a potent protective agent against alcohol-induced gastric injury in the rat - Role of endogenous prostaglandins

David W. Mercer, James M. Cross, Jose C. Barreto, Nathaniel H.P. Strobel, Diane H. Russell, Thomas A. Miller

Research output: Contribution to journalArticle

24 Citations (Scopus)

Abstract

Cholecystokinin is a gastrointestinal hormone known to physiologically regulate pancreatic protein secretion and gallbladder contractility. Some evidence suggests that cholecystokinin is also involved in the maintenance of gastrointestinal mucosal integrity. This study was undertaken to ascertain whether cholecystokinin could prevent the gastric mucosal injury induced by acidified ethanol and what role prostaglandins, and type A and type B cholecystokinin receptors might play in this process. Conscious, fasted rats were given subcutaneous saline or cholecystokinin octapeptide (10-100 μg/kg) 30 min before a l-ml oral gastric bolus of acidified ethanol (150 mM HCl/50% ethanol). Five minutes later, rats were sacrificed and the total area of macroscopic injury quantitated (square millimeters). In additional experiments using a similar protocol, 1 ml of either the cyclooxygenase inhibitor, indomethacin (5 mg/kg), a type A cholecystokinin receptor antagonist, L-364,718 (0.01-1 mg/kg), or the type B cholecystokinin receptor antagonist, L-365,260 (12.5-25 mg/kg) was given intraperitoneally 30 min prior to pretreatment with cholecystokinin octapeptide. Cholecystokinin octapeptide dose-dependently prevented mucosal injury from acidified ethanol (corroborated by histology). The protective effect of cholecystokinin octapeptide was completely negated by L-364,718 and partially reversed by indomethacin, while L-365,260 had no discernible effect in this process. In a further study, cholecystokinin was unable to prevent the damaging effects of aspirin and the inhibition of endogenous prostaglandins. Thus, it appears that cholecystokinin is able to maintain mucosal integrity in the face of a damaging insult by activation of type A cholecystokinin receptors, an effect mediated, at least in part, through the release of endogenous prostaglandins.

Original languageEnglish (US)
Pages (from-to)651-660
Number of pages10
JournalDigestive Diseases and Sciences
Volume40
Issue number3
DOIs
StatePublished - Mar 1 1995

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Protective Agents
Cholecystokinin
Sincalide
Prostaglandins
Stomach
Alcohols
Ethanol
Devazepide
Cholecystokinin A Receptor
Wounds and Injuries
Indomethacin
Prostaglandins B
Cholecystokinin B Receptor
Prostaglandins A
Cholecystokinin Receptors
Gastrointestinal Hormones
Cyclooxygenase Inhibitors
Gallbladder
Aspirin
Histology

Keywords

  • CCK prostaglandins
  • CCK receptors
  • gastric injury

ASJC Scopus subject areas

  • Physiology
  • Gastroenterology

Cite this

Cholecystokinin is a potent protective agent against alcohol-induced gastric injury in the rat - Role of endogenous prostaglandins. / Mercer, David W.; Cross, James M.; Barreto, Jose C.; Strobel, Nathaniel H.P.; Russell, Diane H.; Miller, Thomas A.

In: Digestive Diseases and Sciences, Vol. 40, No. 3, 01.03.1995, p. 651-660.

Research output: Contribution to journalArticle

Mercer, David W. ; Cross, James M. ; Barreto, Jose C. ; Strobel, Nathaniel H.P. ; Russell, Diane H. ; Miller, Thomas A. / Cholecystokinin is a potent protective agent against alcohol-induced gastric injury in the rat - Role of endogenous prostaglandins. In: Digestive Diseases and Sciences. 1995 ; Vol. 40, No. 3. pp. 651-660.
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