cholecystokinin and Hemorrhage

Pancreatic duct obstruction induces edematous but not hemorrhagic pancreatitis even when combined with maximal secretory stimulation. The aim of the present study was to test the hypothesis that pancreatic and bile duct obstruction exacerbates edematous pancreatitis induced by supramaximal secretory stimulation by caerulein.. In in vivo studies using rats, biliopancreatic duct ligation was combined with supramaximal stimulation of caerulein, and pancreatic histology, serum amylase level, pancreatic edema, and intrapancreatic trypsin activation were evaluated. In in vitro studies, the pancreatic acini were isolated from the rats with biliopancreatic duct ligation, and amylase secretion, intracellular trypsin activation, and acinar cell fragility were evaluated.. Biliopancreatic duct ligation exacerbated caerulein-induced pancreatitis from edematous to hemorrhagic only when the obstruction preceded caerulein administration. The amylase secretion from the acini was inhibited, and intracellular trypsin activation and the acinar cell fragility on the supramaximal stimulation with cholecystokinin in vitro were enhanced by the preceding in vivo biliopancreatic duct obstruction.. Preceding biliopancreatic duct obstruction exacerbates caerulein-induced pancreatitis. Enhancement of intracellular trypsin activation is possibly involved in this mechanism.

Topics: Amylases; Animals; Ceruletide; Cholecystokinin; Cholestasis; Constriction, Pathologic; Disease Models, Animal; Disease Progression; Hemorrhage; In Vitro Techniques; Male; Pancreas; Pancreatic Ducts; Pancreatitis; Rats; Rats, Wistar; Trypsin

Cholecystokinin (CCK) plays an important role in regeneration after acute pancreatitis in rats. The present study was aimed to elucidate the role of CCK-1 receptor (CCK-1R) in acute pancreatitis. We investigated the serial changes in CCK-1R mRNA and protein levels and their immunolocalization after acute haemorrhagic pancreatitis induced in male Wistar rats by retrograde intraductal infusion of 4% sodium taurocholate (100 micro L 100 g(-1) body weight).. Histological changes were evaluated by haematoxylin and eosin staining. Pancreatic CCK-1R mRNA was determined by Northern blot analysis. Pancreatic CCK-1R protein was evaluated by immunoblot analysis and immunohistochemistry with a polyclonal antibody against rat CCK-1R protein.. Histological findings revealed that newly formed acinar cells were detected at the periphery of tubular complexes on day 14, and normal architecture of lobules was observed focally on day 21. Pancreatic CCK-1R mRNA peaked on day 3 and thereafter gradually decreased. Cholecystokinin-1R protein rapidly increased after induction of pancreatitits, reaching a maximal level on day 3. On day 3, intense immunoreactivity for CCK-1R protein was observed in both the cytoplasm of vacuolized acinar cells and the tubular complexes. In the regenerative process after acute haemorrhagic pancreatitis in rats, the expression of pancreatic CCK-1R mRNA and protein increased, and intense immunoreactivity for CCK-1R protein was observed in tubular complexes in the cytoplasm of regenerated acinar cells.. These results suggest that CCK-1R contributes to pancreatic regeneration after acute haemorrhagic pancreatitis and that tubular complexes are involved in the process of acinar cell regeneration following pancreatic injury.

Topics: Acute Disease; Animals; Cholecystokinin; Hemorrhage; Male; Pancreas; Pancreatitis; Rats; Rats, Wistar; Receptors, Cholecystokinin; Regeneration; Up-Regulation

The role of endogenous cholecystokinin (CCK) release and exogenous CCK-8 administration in the development and progression of acute pancreatitis and in the early recovery phase of acute pancreatitis were investigated in rats with closed duodenal loop (CDL)-induced pancreatitis. The subcutaneous injection of CCK-8 (2 micrograms/kg) stimulated a physiological level of pancreatic enzyme secretion in normal control rats, but did not lead to any biochemical or histological evidence of acute pancreatitis. A higher dose of CCK-8 (8 micrograms/kg), however, did produce both biochemical and histological evidence of acute pancreatitis in the normal control rats. When 2 micrograms/kg of CCK-8 was injected subcutaneously in rats 6 and 12 h after the creation of the CDL, neither the biochemical nor the histological findings of acute pancreatitis showed any progression compared with the changes in controls given no CCK-8. Serum CCK levels, measured by radio-immunoassay, increased significantly from mean levels of 5.39 pg/ml (+/- 0.95 SD) before creation of the CDL to 42.06 pg/ml (+/- 2.27 SD) 6 h after, and 41.95 pg/ml (+/- 1.88 SD) 12 h after its creation (P < 0.01). The difference between serum CCK levels at 6 and 12 h was not statistically significant. Following the release of the loop, serum CCK levels decreased gradually, especially in rats in which the loop was released 6 h after being created. Although no marked biochemical and histological changes of acute pancreatitis were observed following the administration of 2 micrograms/kg of CCK-8 to rats upon release of the loop 6 h and 12 h after its creation, a higher dose of CCK-8 (8 micrograms/kg) in these rats adversely affected both the biochemical and histological findings of acute pancreatitis. Based on these findings, it was concluded that neither endogenous CCK release, as a result of the CDL, nor physiological stimulation of the pancreas by exogenous CCK-8 administration, caused progression from edematous to hemorrhagic acute pancreatitis, and neither CCK treatment had any adverse effect on the early recovery phase of CDL-induced acute pancreatitis. A pharmacological dose of CCK, however, exacerbated the acute pancreatitis, even in the early recovery stage.

Topics: Acute Disease; Animals; Cholecystokinin; Duodenum; Hemorrhage; Male; Pancreas; Pancreatitis; Rats; Rats, Sprague-Dawley; Sincalide; Time Factors

The aim of this study was to investigate the effect of endogenous cholecystokinin (CCK) on pancreatic regeneration after acute hemorrhagic pancreatitis. Acute hemorrhagic pancreatitis was induced in rats by two intraperitoneal cerulein injection (20 micrograms/kg BW) with 5h water-immersion stress once a day for successive 3 days. After the cessation of repetition of acute pancreatitis the rats were treated with successive feeding with 0.1% camostat-containing diet or SC injection of CR-1505 (CCK receptor antagonist, 50 mg/kg BW x 2/day) for 7 days. Zymogen enzymes and protein contents per DNA in pancreatic tissue were significantly higher in rats treated with camostat compared with control rats, and plasma CCK level was elevated. To the contrary, pancreatic regeneration was retarded in the rats treated with CR 1505. It is concluded that endogenous CCK has a trophic effect during regeneration after acute hemorrhagic pancreatitis.

Topics: Acute Disease; Animals; Cholecystokinin; Hemorrhage; Male; Pancreas; Pancreatitis; Proglumide; Rats; Rats, Sprague-Dawley; Receptors, Cholecystokinin; Regeneration

To determine whether a synthetic somatostatin analogue, octreotide, and a cholecystokinin receptor antagonist, L-364,718, may be beneficial in acute pancreatitis, 33 dogs were assigned to four groups. Each dog underwent laparotomy with injection of autologous bile into the dorsal pancreatic duct. Thirty minutes after the induction of pancreatitis, Group 1 received a subcutaneous injection of octreotide (200 micrograms/kg), Group 2 received an equal volume of the octreotide carrier, Group 3 received an hourly intravenous bolus of L-364,718 (60 micrograms/kg), and Group 4 received an equal volume of the L-364,718 carrier. Hemodynamic profiles, arterial blood gases, plasma glucose, and serum amylase were obtained before laparotomy, at bile injection, and at hourly intervals. The pancreas was removed after 8 hours for gross evaluation, measurement of water content, and histologic examination. A significant decrease in cardiac index and a significant increase in serum amylase and pancreatic edema occurred in all four groups 8 hours after the induction of pancreatitis (P less than 0.05), but there was no statistical difference between any group. Likewise, there was no difference in gross or histologic changes in the pancreas of any group. The somatostatin analogue, octreotide, and the cholecystokinin receptor antagonist, L-364,718, did not ameliorate the effects of severe, bile-induced pancreatitis in dogs.

Topics: Acute Disease; Amylases; Animals; Benzodiazepinones; Bile; Body Water; Cardiac Output; Cholecystokinin; Devazepide; Dogs; Edema; Hemorrhage; Injections, Intravenous; Injections, Subcutaneous; Necrosis; Octreotide; Pancreas; Pancreatitis

In an experimental model of bleeding-induced hypovolemic shock causing the death of all saline-treated rats within 26 +/- 4 min, the intravenous injection of bombesin (2.5, 5 or 10 micrograms/kg) dose-dependently restored blood pressure, pulse amplitude, heart rate and respiratory function, and improved survival rate as assessed at the end of the experiment (2 h). The effect on cardiovascular and respiratory functions was prompt (within 1-2 min) and sustained. The release of cholecystokinin seems to be the main mechanism of action, because the anti-shock effect of bombesin is largely prevented by the CCK-antagonist, L-364,718.

Topics: Animals; Benzodiazepinones; Blood Pressure; Bombesin; Cholecystokinin; Devazepide; Female; Hemorrhage; Injections, Intravenous; Male; Pulse; Rats; Rats, Inbred Strains; Respiration; Shock

Asperlicin (ASP), a new, nonpeptidal cholecystokinin (CCK) receptor antagonist isolated from the fungus Aspergillus alliaceus, has an affinity that is 300-400 times greater than that of proglumide for gallbladder, ileal, and pancreatic CCK receptors. The long in vivo half-life and high selectivity for peripheral CCK receptors make ASP suitable for investigations on the physiological and pharmacological actions of CCK. Endogenous CCK has been postulated to participate in the pathogenesis of acute hemorrhagic pancreatitis (AHP) in rats and mice. We examined the effects of ASP in rats on the early course (6 h) of AHP induced by a retrograde infusion of sodium taurocholate (NaTC) into the common bile-pancreatic duct. An i.v. bolus injection of ASP (either 10 mg/kg or 30 mg/kg) in dimethyl sulfoxide (DMSO) given 1 h prior to AHP induction failed to significantly alter pancreas weights, serum amylase concentrations, or pancreatic histopathology when compared with AHP control rats treated with vehicle alone. However, rats given 2 i.p. injections of ASP (either 20 mg/kg/injection or 40 mg/kg/injection) in DMSO: olive oil 1 h before and 2 h after induction of AHP exhibited significantly reduced serum amylase concentrations. Additionally, rats given the high dose i.p. injections of ASP also had significantly reduced pancreas weights and less severe pancreas histopathology compared with AHP control animals. These data indicate that endogenous CCK participates in the pathogenesis of NaTC-induced AHP in the rat.

Topics: Acute Disease; Amylases; Animals; Benzodiazepinones; Cholecystokinin; Dimethyl Sulfoxide; Hemorrhage; Male; Olive Oil; Organ Size; Pancreatitis; Pharmaceutical Vehicles; Plant Oils; Rats; Rats, Inbred Strains; Receptors, Cholecystokinin; Taurocholic Acid

The effects of the cholecystokinin (CCK)-receptor antagonist proglumide, the protease inhibitor gabexate, and the hormones secretin and cholecystokinin-octapeptide (CCK-8) were studied in a model of acute hemorrhagic pancreatitis induced by feeding mice a choline-deficient, ethionine-supplemented (CDE) diet. Injections of gabexate and proglumide from initiation of CDE diet (before induction of pancreatitis) increased survival from 37% (diet alone) to 85 and 75%, respectively, and also ameliorated histological alterations and increases in serum amylase concentration and pancreatic activated trypsin. Secretin had no major beneficial effect. When proglumide or gabexate were given after induction of pancreatitis, proglumide still increased survival to 75%, whereas gabexate no longer did. Injection of nontoxic doses of CCK-8 before proglumide or gabexate injections completely abolished all beneficial effects and also increased the severity of pancreatitis due to CDE diet alone. Blockade of CCK receptors and early inhibition of protease activity may be beneficial in severe acute pancreatitis. Cholecystokinin appears to play a contributory role in the development of pancreatitis.

Topics: Acute Disease; Amylases; Animals; Cholecystokinin; Choline Deficiency; Disease Models, Animal; Ethionine; Female; Gabexate; Guanidines; Hemorrhage; Mice; Pancreas; Pancreatitis; Proglumide; Receptors, Cholecystokinin; Secretin; Time Factors; Trypsin