Involvement of cholecystokinin receptors in the adverse effect of glucocorticoids on diet-induced necrotizing pancreatitis

Guillermo Gomez, Courtney Townsend, Daniel Green, Srinivasan Rajaraman, Tatsuo Uchida, James C. Thompson

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

The mechanism that explains the association between corticoids and acute pancreatitis is unknown. Our hypothesis was that chronic glucocorticoid treatment could adversely affect the course of hemorrhagic pancreatitis by acting through cholecystokinin (CCK) receptors. Acute necrotizing pancreatitis was induced by feeding young female mice a choline-deficient, ethionine-supplemented (CDE) diet for 60 hours. Treatment with hydrocortisone (10 mg/kg/day) was begun 1 week before pancreatitis. At the onset of the CDE diet, a group of hydrocortisone-treated mice were also given the CCK receptor antagonist CR-1409 (5 mg/kg three times a day). Control mice received injections of saline solution. A follow-up of 336 hours was conducted for survival analysis. Hydrocortisone given alone did not produce pancreatitis. Hydrocortisone, however, did increase the pancreatic necrosis caused by the CDE diet (from 40% to 70%) and significantly reduce survival (from 40% to 9%). CR-1409 completely abolished the adverse effects of hydrocortisone on pancreatitis. We measured amylase release by dispersed pancreatic acini from mice chronically treated with hydrocortisone m response to CCK-8. Treatment with hydrocortisone increased both the sensitivity and the responsiveness of the pancreas to CCK-8. We conclude that glucocorticoids alone may not induce acute pancreatitis, but they can increase the risk of a more severe form of pancreatitis developing. The glucocorticoid effect appears to be attributable to a CCK receptor-mediated sensitization of the pancreas to endogenous CCK. Thus, CCK-receptor blockade may improve survival in necrotizing pancreatitis associated with chronic glucocorticoid treatments.

Original languageEnglish (US)
Pages (from-to)230-238
Number of pages9
JournalSurgery
Volume106
Issue number2
StatePublished - 1989

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Cholecystokinin Receptors
Pancreatitis
Glucocorticoids
Hydrocortisone
Diet
Ethionine
Choline
Pancreas
Acute Necrotizing Pancreatitis
Cholecystokinin
Therapeutics
Amylases
Survival Analysis
Sodium Chloride
Adrenal Cortex Hormones
Necrosis
Injections

ASJC Scopus subject areas

  • Surgery

Cite this

Gomez, G., Townsend, C., Green, D., Rajaraman, S., Uchida, T., & Thompson, J. C. (1989). Involvement of cholecystokinin receptors in the adverse effect of glucocorticoids on diet-induced necrotizing pancreatitis. Surgery, 106(2), 230-238.

Involvement of cholecystokinin receptors in the adverse effect of glucocorticoids on diet-induced necrotizing pancreatitis. / Gomez, Guillermo; Townsend, Courtney; Green, Daniel; Rajaraman, Srinivasan; Uchida, Tatsuo; Thompson, James C.

In: Surgery, Vol. 106, No. 2, 1989, p. 230-238.

Research output: Contribution to journalArticle

Gomez, G, Townsend, C, Green, D, Rajaraman, S, Uchida, T & Thompson, JC 1989, 'Involvement of cholecystokinin receptors in the adverse effect of glucocorticoids on diet-induced necrotizing pancreatitis', Surgery, vol. 106, no. 2, pp. 230-238.
Gomez, Guillermo ; Townsend, Courtney ; Green, Daniel ; Rajaraman, Srinivasan ; Uchida, Tatsuo ; Thompson, James C. / Involvement of cholecystokinin receptors in the adverse effect of glucocorticoids on diet-induced necrotizing pancreatitis. In: Surgery. 1989 ; Vol. 106, No. 2. pp. 230-238.
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