cholecystokinin and Edema

Topics: Animals; Axonal Transport; Axons; Capsaicin; Cholecystokinin; Edema; Fatty Acids, Unsaturated; Ganglia, Spinal; Nerve Degeneration; Nerve Fibers; Neurons, Afferent; Pain; Rats; Reflex; Sensation; Substance P

In contrast to supramaximal CCK-8 or caerulein, acute or prolonged supraphysiological levels of endogenous CCK-58 do not cause pancreatitis. Compared with CCK-8, CCK-58 is a much stronger stimulant of pancreatic chloride and water secretion, equivalent to maximally effective secretin, but with a chloride-to-bicarbonate ratio characteristic of acinar fluid. Because supraphysiological endogenous CCK does not cause pancreatitis and because coadministration of secretin ameliorated caerulein- or CCK-8-induced pancreatitis, coincident with restoring pancreatic water secretion, we hypothesized that supramaximal CCK-58 would not induce pancreatitis. Conscious rats were infused intravenously with 2 or 4 nmol x kg(-1) x h(-1) of CCK-8 or synthetic rat CCK-58 for 6 h, and pancreases were examined for morphological and biochemical indexes of acute pancreatitis. A second group was treated as above while monitoring pancreatic protein and water secretion. CCK-8 at 2 nmol x kg(-1) x h(-1) caused severe edematous pancreatitis as evidenced by morphological and biochemical criteria. CCK-58 at this dose had minimal or no effect on these indexes. CCK-58 at 4 nmol x kg(-1) x h(-1) increased some indexes of pancreatic damage but less than either the 2 or 4 nmol x kg(-1) x h(-1) dose of CCK-8. Pancreatic water and protein secretion were nearly or completely abolished within 3 h of onset of CCK-8 infusion, whereas water and protein secretion were maintained near basal levels in CCK-58-treated rats. We hypothesize that supramaximal CCK-58 does not induce pancreatitis because it maintains pancreatic acinar chloride and water secretion, which are essential for exocytosis of activated zymogens. We conclude that CCK-58 may be a valuable tool for investigating events that trigger pancreatitis.

Topics: Amylases; Animals; Body Water; Chlorides; Cholecystokinin; Dose-Response Relationship, Drug; Edema; Interleukin-6; Male; Organ Size; Pancreas; Pancreatic Juice; Pancreatitis; Peroxidase; Rats; Rats, Wistar; Secretory Rate; Sincalide; Time Factors; Trypsin; Trypsinogen

Obstruction-induced acute pancreatitis in rats is associated with increased plasma cholecystokinin (CCK) levels. Duodenal replacement of bile reduces severity of pancreatitis and limits CCK increase. We investigated the role of CCK in the pathogenesis of obstruction-induced acute pancreatitis by pretreating rats with the somatostatin analog octreotide and the CCK antagonist L-364,718. Octreotide inhibits duodenal CCK release, and L-364,718 competitively blocks CCK receptors. We studied 31 rats after (1) sham operation (n = 7), (2) bile and pancreatic duct obstruction (BPDO) (n = 12), (3) BPDO plus octreotide (20 micrograms/kg IP and then 5 micrograms/kg/hr IV) (n = 6), and (4) BPDO plus L-364,718 (1 mg/kg IP and then 0.25 mg/kg/hr IV) (n = 6). Rats were killed after 18 hours. Pancreas weight, acute pancreatitis histology score, and plasma amylase and CCK levels were determined. Octreotide and L-364,718 limited the increase in pancreas weight. Octreotide also limited the rise in plasma CCK levels. These findings suggest that CCK may play a role in the pathogenesis of obstruction-induced acute pancreatitis.

Topics: Acute Disease; Analysis of Variance; Animals; Benzodiazepinones; Bile Ducts; Cholecystokinin; Devazepide; Edema; Male; Octreotide; Pancreas; Pancreatic Ducts; Pancreatitis; Rats; Rats, Sprague-Dawley

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 studies on the pathogenesis of ischemic cell injury and of other pancreatic diseases the knowledge of the actual pancreatic energy state is an important factor. Therefore, it would be advantageous to have a simple and inexpensive method to determine this parameter and its alterations in the pancreas. At uniform hormonal stimulation, the extent of exocrine pancreatic secretion showed a clear dependence on energy supply in this organ. The degree of pancreatic juice edema formed after bolus injection of cholecystokinin and secretin at ductal occlusion was found to be the most sensitive and reproducible measure of the functional capacity of the pancreatic energy metabolism. While this parameter can be applied to experimental studies, only, the juice volume secreted could be determined under clinical conditions, too. Both parameters of pancreatic secretion were clearly decreased after preceding short-term ischemia and recovered after an adequate interval of reperfusion.

Topics: Animals; Cholecystokinin; Dose-Response Relationship, Drug; Edema; Energy Metabolism; Female; Ischemia; Pancreas; Pancreatic Diseases; Pancreatic Juice; Rats; Secretin

Topics: Acute Disease; Cholecystokinin; Duodenum; Edema; Humans; Intestinal Secretions; Pancreas; Pancreatic Juice; Pancreatitis; Secretin

Topics: Amylases; Animals; Cholecystokinin; Dogs; Edema; In Vitro Techniques; Lipase; Pancreas; Pancreatectomy; Perfusion; Secretin; Trypsin