1995 Fiscal Year Final Research Report Summary
Pathophysiological role of CCK in acute experimental pancreatitis
| Project/Area Number |
06670573
|
|---|
| Research Category |
Grant-in-Aid for General Scientific Research (C)
|
| Allocation Type | Single-year Grants |
|---|
| Research Field |
Gastroenterology
|
|---|
| Research Institution | Kyoto Prefectural University of Medicine |
|---|
Principal Investigator |
KASHIMA Kei Kyoto Prefectural University of Medicine, Department of Internal Medicine, Professor, 医学部, 教授 (30079818)
|
|---|
| Co-Investigator(Kenkyū-buntansha) |
KATAOKA Keisho Kyoto Prefectural University of Medicine, Department of Internal Medicine, Assis, 医学部, 助手 (70185792)
|
|---|
| Project Period (FY) |
1994 – 1995
|
| Keywords | Experimantal pancreatitis / CCK / Acinar cell regeneration / PCNA / BrdU / The subcellular fractionation / Cathepsin B / CCK receptor antagonist |
|---|
| Research Abstract |
During 14 days in rats with arginine-induced acute pancreatitis, acinar cell regener ation was estimated by using immunogold-silver staining with anti-PCNA or anti-Br dU antibody. PCNA labeling index (L.I.), that was expressed as percentage of PCNA positive cells in 1000 acinar cells, indicated two major peaks on day 0.5 and 7 as well as Br dU L.I.Plasma CCK bioactivities which increased rapidly following the onset of acute pancreatitis reached the peak on day 3, and then continued high levels during 11 days. Increased levels of plasma CCK significantly correlated with Br dU L.I.during regenerative phase of acute pancreatitis. Furthermore, long-term administration of CR1505, a CCK receptor antagonist, apparently suppressed not only normal pancreatic growth but also acinar regeneration following acute pancreatitis. Based in these data, it is concluded that endogenous CCK plays an important role in acinar cell proliferation even in acute pancreatitis. We investigated also an role of CCK in intracellular pathogenesis of acute pancreatitis by using the method of the subcellular fractionation. In both caerulein- and arginine-induced pancreatitis, we found the redistribution of cathepsin B into zymogen fraction. Subsequent activation of trypsinogen to trypsin was recognized in arginine-pancreatitis but not in caerulein-pancreatitis. CR1505 caused minor improvement of the redistribution of cathepsin B in both model. Protective effect of CR1505 on acute pancreatitis was obtained in caerulein-pancreatitis and not in arginine-pancreatitis. The role of CCK on the pathophysiology of acute pancreatitis was clarified in the present study but we should study further the intracellular events in acinar cells in acutepancreatitis.
|
