Pancreatic regeneration after ethionine-induced acute pancreatitis in rats lacking pancreatic CCK-A receptor gene expression.
BACKGROUND
We examined the effects of cholecystokinin (CCK) on the development of ethionine-induced pancreatitis and pancreatic recovery. We used Otsuka Long-Evans Tokushima Fatty (OLETF) rats, a model lacking pancreatic CCK-A receptor gene expression.


METHODS
Ethionine-induced pancreatitis was induced in the 7-week-old male OLETF rats and in a control group that does not lack the pancreatic CCK-A receptor, Long-Evans Tokushima Otsuka (LETO) rats. The two groups were maintained on a low-protein diet for 11 days. During the last 4 days of the low-protein diet, dl-ethionine 20 mg/100 g body weight was administered intraperitoneally once daily. Histologic and biochemical examinations of the pancreas were performed, and plasma CCK concentrations were measured on days 1, 4, and 7 after the last ethionine administration.


RESULTS
Pancreatic histologic scores for inflammation, hemorrhage, and necrosis in the LETO and OLETF rats were highest on days 1 and 4, respectively. Pancreatic weight, DNA content, and protein level per DNA content in both groups decreased during the low-protein diet, and recovery signs were delayed in the OLETF rats. The highest plasma CCK concentrations in the LETO and OLETF rats were reached on days 1 and 4, respectively.


CONCLUSIONS
Ethionine-induced pancreatitis developed in the OLETF rats, and their pancreatic regeneration was delayed in comparison to that in the LETO rats. Our results suggested that CCK plays an important role in the development of pancreatitis as well as in the pancreatic repair process.
Sato
Takaya
T
Second Department of Internal Medicine, Showa University School of Medicine, 1-5-8 Hatanodai, Shinagawa-ku, Tokyo 142-8666, Japan.
Niikawa
Junichi
J
Usui
Ichiro
I
Imamura
Tsunao
T
Yoshida
Hitoshi
H
Tanaka
Shigeki
S
Mitamura
Keiji
K
D000818:Animals; D002766:Cholecystokinin / Q000097:blood; D004247:DNA / Q000032:analysis; D005001:Ethionine; D015870:Gene Expression; D008297:Male; D010179:Pancreas / Q000737:chemistry / Q000473:pathology / Q000502:physiology*; D019283:Pancreatitis, Acute Necrotizing / Q000139:chemically induced / Q000235:genetics / Q000473:pathology / Q000503:physiopathology*; D011506:Proteins / Q000032:analysis; D051381:Rats; D020334:Rats, Inbred OLETF; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin / Q000235:genetics* / Q000502:physiology; D012038:Regeneration
D011506:Proteins; D043886:Receptor, Cholecystokinin A; D011949:Receptors, Cholecystokinin; D004247:DNA; D002766:Cholecystokinin; D005001:Ethionine