Severe subcellular damage in the rat exocrine pancreas after pancreatobiliary diversion.
Cholecystokinin (CCK) may contribute to the genesis of both pancreatic carcinoma and acute pancreatitis. By transposing a long segment of jejunum to lie between the pylorus and the duodenal papilla, pancreatobiliary diversion (PBD) causes a persistent increase in circulating CCK levels, as the normal feedback inhibition of jejunal CCK release by pancreatic juice is evaded. A number of morphological, physiological, and acinar cytokinetic changes ensue. This investigation has examined the ultrastructural changes in pancreatic acinar cells after PBD in the presence and absence of CR1409 (lorglumide), a CCK receptor antagonist. After 14 days there was degranulation and vacuolation of acinar cells with involvement of the enzyme acid phosphatase. The presence of morphologically distinct extracisternal acid phosphatase indisputably predisposed acinar cells to severe damage. Treatment with CR1409 largely prevented degranulation after PBD, but vacuolation of acinar cells still occurred, indicating a possible toxic effect of the receptor antagonist. This is the first report of CCK itself, rather than one of its analogues, causing in vivo pancreatic damage that is generally considered as a forerunner to acute pancreatitis. This is of fundamental importance to the understanding of the earliest stages of the disease.
Sarraf
C E
CE
Department of Histopathology, Royal Postgraduate Medical School, Hammersmith Hospital, London, England.
Watanapa
P
P
Emons
V E
VE
Williamson
R C
RC
Alison
M R
MR
D000135:Acid Phosphatase / Q000032:analysis; D000818:Animals; D001652:Bile Ducts / Q000601:surgery*; D002766:Cholecystokinin / Q000097:blood*; D008297:Male; D008854:Microscopy, Electron; D010179:Pancreas / Q000473:pathology / Q000648:ultrastructure*; D010183:Pancreatic Ducts / Q000601:surgery*; D011377:Proglumide / Q000031:analogs & derivatives / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar
D002766:Cholecystokinin; D000135:Acid Phosphatase; D011377:Proglumide; C048181:lorglumide