TY - JOUR
T1 - Cholecystokinin Augmentation of 'Surgical' Pancreatitis
T2 - Benefits of Receptor Blockade
AU - Modlin, Irvin M.
AU - Bilchik, Anton J.
AU - Zucker, Karl A.
AU - Adrian, Thomas E.
AU - Sussman, Jeffrey
AU - Graham, Scott M.
PY - 1989/5
Y1 - 1989/5
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=0024514040&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0024514040&partnerID=8YFLogxK
U2 - 10.1001/archsurg.1989.01410050064013
DO - 10.1001/archsurg.1989.01410050064013
M3 - Article
C2 - 2469410
AN - SCOPUS:0024514040
SN - 2168-6254
VL - 124
SP - 574
EP - 578
JO - JAMA Surgery
JF - JAMA Surgery
IS - 5
ER -