title: Effect of endogenous cholecystokinin on the course of acute pancreatitis in rats.
abstract: OBJECTIVE
  To examine the effects of pancreatic rest, stimulation and rest/stimulation on the natural course of recovery after acute pancreatitis.
  
  
  METHODS
  Acute hemorrhagic pancreatitis (AP) was induced in male rats by intraductal infusion of 40 μL/100 g body weight of 3% sodium taurocholate. All rats took food ad libitum. At 24 h after induction of AP, rats were divided into four groups: control (AP-C), pancreas rest (AP-R), stimulation (AP-S), and rest/stimulation (AP-R/S). Rats in the AP-C, AP-R and AP-S groups received oral administration of 2 mL/kg body weight saline, cholecystokinin (CCK)-1 receptor antagonist, and endogenous CCK release stimulant, respectively, twice daily for 10 d, while those in the AP-R/S group received twice daily CCK-1 receptor antagonist for the first 5 d followed by twice daily CCK release stimulant for 5 d. Rats without any treatment were used as control group (Control). Biochemical and histological changes in the pancreas, and secretory function were evaluated on day 12 at 24 h after the last treatment.
  
  
  RESULTS
  Feeding ad libitum (AP-C) delayed biochemical, histological and functional recovery from AP. In AP-C rats, bombesin-stimulated pancreatic secretory function and HOMA-β-cell score were significantly lower than those in other groups of rats. In AP-R rats, protein per DNA ratio and pancreatic exocrine secretory function were significantly low compared with those in Control rats. In AP-S and AP-R/S rats, the above parameters recovered to the Control levels. Bombesin-stimulated pancreatic exocrine response in AP-R/S rats was higher than in AP-S rats and almost returned to control levels. In the pancreas of AP-C rats, destruction of pancreatic acini, marked infiltration of inflammatory cells, and strong expression of α-smooth muscle actin, tumor necrosis factor-α and interleukin-1β were seen. Pancreatic rest reversed these histological alterations, but not atrophy of pancreatic acini and mild infiltration of inflammatory cells. In AP-S and AP-R/S rats, the pancreas showed almost normal architecture.
  
  
  CONCLUSIONS
  The favorable treatment strategy for AP is to keep the pancreas at rest during an early stage followed by pancreatic stimulation by promoting endogenous CCK release.
authors.affiliation: Dongmei Jia, Department of Gastroenterology and Metabolism, University of Occupational and Environmental Health, Japan, School of Medicine, Kitakyushu 807-8555, Japan.
authors.forename: Dongmei
authors.initials: D
authors.lastname: Jia
authors.affiliation: Dongmei Jia, Department of Gastroenterology and Metabolism, University of Occupational and Environmental Health, Japan, School of Medicine, Kitakyushu 807-8555, Japan.
authors.forename: Mitsuyoshi
authors.initials: M
authors.lastname: Yamamoto
authors.affiliation: Dongmei Jia, Department of Gastroenterology and Metabolism, University of Occupational and Environmental Health, Japan, School of Medicine, Kitakyushu 807-8555, Japan.
authors.forename: Makoto
authors.initials: M
authors.lastname: Otsuki
mesh_terms: D000284:Administration, Oral; D000818:Animals; D015415:Biomarkers / Q000097:blood; D001839:Bombesin / Q000008:administration & dosage; D049109:Cell Proliferation; D002766:Cholecystokinin / Q000378:metabolism*; D004261:DNA Replication; D004195:Disease Models, Animal; D004952:Esters; D016670:Gabexate / Q000008:administration & dosage / Q000031:analogs & derivatives; D006146:Guanidines; D006727:Hormone Antagonists / Q000008:administration & dosage; D007333:Insulin Resistance; D008297:Male; D010179:Pancreas / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D010186:Pancreatic Function Tests; D010195:Pancreatitis / Q000139:chemically induced / Q000175:diagnosis / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D011377:Proglumide / Q000008:administration & dosage / Q000031:analogs & derivatives; D017208:Rats, Wistar; D043886:Receptor, Cholecystokinin A / Q000037:antagonists & inhibitors / Q000378:metabolism; D020127:Recovery of Function; D013656:Taurocholic Acid; D013997:Time Factors
chemical_list: D015415:Biomarkers; D004952:Esters; D006146:Guanidines; D006727:Hormone Antagonists; D043886:Receptor, Cholecystokinin A; C034532:camostat; D016670:Gabexate; D013656:Taurocholic Acid; C053737:loxiglumide; D002766:Cholecystokinin; D011377:Proglumide; D001839:Bombesin
keywords: Acute pancreatitis; Cholecystokinin; Pancreatic function; Pancreatic rest; Pancreatic stimulation