Cholecystokinin augmentation of 'surgical' pancreatitis. Benefits of receptor blockade.
The management of acute pancreatitis has not changed appreciably throughout several decades. Recent evidence has suggested that cholecystokinin (CCK) may play an important role in pancreatic disease. Investigations into the precise role of CCK in acute pancreatitis have been hampered by the lack of a specific CCK receptor antagonist. Using a newly described, highly potent and specific CCK receptor antagonist, L-364,718, the effect of CCK in two models of acute "surgical" pancreatitis was examined: (1) the bile salt ductal perfusion model in the rat and (2) a traumatic model in the guinea pig. At a suboptimal dose for pancreatic enzyme secretion (25 pmol/kg/h), CCK was found to potentiate the severity of the ensuing pancreatitis in both models. Continuous CCK receptor blockade with L-364,718 (25 nmol/kg/h) improved biochemical, morphologic, and survival indexes. This study suggests that physiologic levels of CCK play an important permissive role in the evolution of acute pancreatitis. The use of L-364,718 as an investigative probe or therapeutic tool for acute pancreatitis is worthy of further consideration.
Modlin
I M
IM
Gastrointestinal Surgical Research Group, Yale University School of Medicine, New Haven, CT 06510.
Bilchik
A J
AJ
Zucker
K A
KA
Adrian
T E
TE
Sussman
J
J
Graham
S M
SM
D000208:Acute Disease; D000681:Amylases / Q000097:blood; D000818:Animals; D001570:Benzodiazepinones / Q000494:pharmacology*; D002766:Cholecystokinin / Q000037:antagonists & inhibitors* / Q000502:physiology; D020109:Devazepide; D005260:Female; D006168:Guinea Pigs; D008049:Lipase / Q000097:blood; D008297:Male; D009336:Necrosis; D009929:Organ Size; D010179:Pancreas / Q000473:pathology; D010195:Pancreatitis / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology; D051381:Rats; D011919:Rats, Inbred Strains
D001570:Benzodiazepinones; D002766:Cholecystokinin; D008049:Lipase; D000681:Amylases; D020109:Devazepide