Supramaximal CCK-58 does not induce pancreatitis in the rat: Role of pancreatic water secretion

Mitsuyoshi Yamamoto, Joseph R. Reeve, Gary M. Green

Research output: Contribution to journalArticlepeer-review

14 Scopus citations

Abstract

In contrast to supramaximal CCK-8 or caerulein, acute or prolonged supraphysiological levels of endogenous CCK-58 do not cause pancreatitis. Compared with CCK-8, CCK-58 is a much stronger stimulant of pancreatic chloride and water secretion, equivalent to maximally effective secretin, but with a chloride-to-bicarbonate ratio characteristic of acinar fluid. Because supraphysiological endogenous CCK does not cause pancreatitis and because coadministration of secretin ameliorated caerulein- or CCK-8-induced pancreatitis, coincident with restoring pancreatic water secretion, we hypothesized that supramaximal CCK-58 would not induce pancreatitis. Conscious rats were infused intravenously with 2 or 4 nmol·kg -1·h-1 of CCK-8 or synthetic rat CCK-58 for 6 h, and pancreases were examined for morphological and biochemical indexes of acute pancreatitis. A second group was treated as above while monitoring pancreatic protein and water secretion. CCK-8 at 2 nmol·kg -1·h-1 caused severe edematous pancreatitis as evidenced by morphological and biochemical criteria. CCK-58 at this dose had minimal or no effect on these indexes. CCK-58 at 4 nmol·kg -1·h-1 increased some indexes of pancreatic damage but less than either the 2 or 4 nmol·kg-1·h -1 dose of CCK-8. Pancreatic water and protein secretion were nearly or completely abolished within 3 h of onset of CCK-8 infusion, whereas water and protein secretion were maintained near basal levels in CCK-58-treated rats. We hypothesize that supramaximal CCK-58 does not induce pancreatitis because it maintains pancreatic acinar chloride and water secretion, which are essential for exocytosis of activated zymogens. We conclude that CCK-58 may be a valuable tool for investigating events that trigger pancreatitis.

Original languageEnglish (US)
Pages (from-to)G964-G974
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume292
Issue number4
DOIs
StatePublished - Apr 2007

Keywords

  • Acinar fluid secretion
  • Cholecystokinin 58
  • Cholecystokinin 8
  • Pancreatic chloride secretion
  • Pancreatic fluid secretion

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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