Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Acute pancreatitis can be induced in the rat by high doses of cerulein, a cholecystokinin analogue. Regeneration of the pancreatic gland after this aggression can be accelerated by endogenous or exogenous cholecystokinin. However, the biochemical and molecular events associated with the cholecystokinin-induced regeneration process have not yet been identified. This study was therefore undertaken to determine the potential involvement of particulate and crude cytosolic tyrosine kinases as well as phospholipase D (PLD) in the course of pancreatitis induction and during regeneration. Acute pancreatitis was induced by cerulein, 12 micrograms kg-1, every 8 h for 2 days; this treatment was followed by 3 days of rest, and the regeneration treatment was started on the morning of the sixth day, with cerulein given at 1 microgram kg-1 every 8 h for 1-4 days. Animals were sacrificed 1, 3, 6, 12, 24, and 48 h after the first cerulein injection (high dose), on the morning of the sixth day (end of the rest period), and on the morning of the seventh and tenth days (low dose, regeneration period). After sacrifice, pancreata were excised and prepared for tyrosine kinase and PLD assays. Parallel increases in tyrosine kinase and PLD activities were observed from 6 to 48 h during pancreatitis induction and at the end of the resting period. Activities returned to control values during the regeneration period in the untreated cerulein-pancreatitis groups.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Dynamics of pancreatic tyrosine kinase and phospholipase D activities in the course of cerulein-induced acute pancreatitis and during regeneration. 779 95

The effect of long term administration of a synthetic cholecystokinin (CCK) receptor antagonist CR1505 (loxiglumide) on pancreatitis was examined in rats after pancreatic duct ligation (PL) with an internal bile fistula. All rats were given both 6 mg/day of CR1505 continuously infused intraduodenally with an osmotic pump and 32 mg/day introduced into the stomach with an orogastric tube. Rats were killed 7, 14, and 28 days after PL, and changes of body weight, pancreatic wet weight, daily food intake, pancreatic protein content, and histology, plasma amylase concentration, and both plasma and duodenal CCK concentrations were examined. Administration of CR1505 for 7 days from immediately after PL, resulted in decrease of body weight, increase of daily food intake, and significant increases of intestinal CCK concentration and the level of CCK mRNA. However, its administration from day 7 to day 14 or 28 did not improve any of the parameters examined except inflammatory infiltration of the pancreas on the 14th postoperative day. These results suggest that CR1505 may have a beneficial effect on recovery from pancreatitis when administered during the early stage, but not when administered during a later stage.
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PMID:Lack of effect of cholecystokinin receptor antagonist (CR1505) on recovery of experimental pancreatitis after pancreatic duct occlusion in rats. 780 19

In vivo stimulation of the exocrine pancreas with concentrations of secretagogue in excess of a maximally stimulating dose causes a marked disturbance of the intracellular segregation, transport, and exocytosis of digestive enzyme zymogens. Under physiological conditions elements of the cytoskeleton, most notably microtubules and microfilaments, are involved in the regulation of these intracellular events. We infused caerulein, a peptide analogue of cholecystokinin, at a supramaximal dose (10 micrograms.kg-1.h-1 for up to 6 h) intravenously in rats. To study the ultrastructural alterations of acinar cell microfilaments and microtubules by immunogold labeling, we used monoclonal antibodies directed against actin and beta-tubulin. As early as 30 min after the start of the secretagogue infusion we found a progressive disassembly of microtubules and microfilaments in exocrine cells. In immunoblot studies this disassembly of the cytoskeleton was paralleled by a degradation of its structural proteins actin and beta-tubulin. Our results indicate that the earliest morphological events during supramaximal secretagogue stimulation of the pancreas involve the disassembly and degradation of microtubules and microfilaments. This cell biological phenomenon offers an explanation for the disturbances of segregation, transport, and exocytosis of digestive enzymes, which are known to be associated with supramaximal stimulation of the pancreas and experimental models of pancreatitis.
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PMID:Disassembly of rat pancreatic acinar cell cytoskeleton during supramaximal secretagogue stimulation. 786 30

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.
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PMID:Octreotide and cholecystokinin antagonist reduce edema in obstruction-induced acute pancreatitis. 822 60

The usual technique of collecting gallbladder bile at laparotomy is not suitable for sequential studies of cholesterol nucleation time (NT) in patients receiving therapy to prevent or dissolve cholesterol gallstones. Our aim was to study the feasibility of measuring NT in bile obtained by nasobiliary or nasoduodenal intubation. We studied a total of 10 cholesterol gallstone patients; in 8 bile was collected by nasobiliary drainage, in 7 it was collected by nasoduodenal intubation, and in 3 it was collected at laparotomy the next day. Three patients developed abdominal pain and increased serum amylase after endoscopic retrograde cannulation. All three biles obtained at operation nucleated quickly (NT, 1-4 days), whereas duodenal biles were all beyond the expected range (NT, > 21 days). Chymotrypsin activity, as a marker of pancreatic juice contamination, was detected in five of eight nasobiliary biles and in all seven duodenal biles but in none of the surgical biles. Free fatty acids (reflecting lipolysis) were significantly higher in duodenal than in surgical biles, with nasobiliary bile showing intermediate values. Nasobiliary bile showed either a rapid (median NT, 3 days) or a slow (median NT, 22 days) NT, depending on whether chymotrypsin activity was absent or present (p < 0.05). We conclude that duodenal bile is never suitable for NT determination because of contamination by pancreatic enzymes, and that nasobiliary bile, if not contaminated by pancreatic enzymes, may be suitable for NT determination but that its collection via a nasobiliary tube after cholecystokinin injection carries a risk of pancreatitis.
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PMID:Cholesterol nucleation time measurement in nasobiliary or nasoduodenal bile. Comparison with surgical bile. 823 37

KSG-504, a new synthetic cholecystokinin (CCK) receptor antagonist derived from proglumide, has superior selectivity and affinity to CCK-A receptors. We have investigated the effect of KSG-504 on ethionine-induced acute pancreatitis in rats and the influence of endogenous CCK on evolution of pancreatitis and regeneration of pancreatic acinar cells. Reduction of pancreatic proteins and digestive enzyme contents was dose-dependently prevented by subcutaneous administration of KSG-504. The inhibition of evolution of pancreatitis was demonstrated histologically in KSG-504 treated rats. The effect of KSG-504 on pancreatic regeneration was evaluated by bromodeoxyuridine labeling index (B.L.I.) of acinar cells. There was no significant difference of B.L.I. between KSG-504 treated and non-treated rats. These results suggest that KSG-504 has a beneficial effect on ethionine-induced acute pancreatitis by blockade of endogenous CCK.
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PMID:[Effect of KSG-504, a new synthetic cholecystokinin receptor antagonist on ethionine-induced acute pancreatitis in rats]. 828 14

Edematous pancreatitis was induced in 12 male Sprague-Dawley rats using supramaximal doses of the cholecystokinin analogue cerulein (5 micrograms/kg per hour). The microvasculature of the pancreas, liver, and kidney was examined using scanning electron microscopy of microvascular corrosion casts in 12 test animals and four controls at intervals of 30 minutes, 1 hour, 2 hours, and 4 hours. Distortion of the pancreatic and hepatic microvasculature was seen as early as 30 minutes and progressed during the study period. The renal vasculature remained normal throughout. Light microscopic analysis revealed no morphologic abnormalities in the walls of the pancreatic, hepatic, or renal microvasculature. This study demonstrates that cerulein-induced pancreatitis is associated with marked distortion of the pancreatic and hepatic microvasculature; the abnormalities start early in the disease and progress during the study period.
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PMID:Microvasculature of the pancreas, liver, and kidney in cerulein-induced pancreatitis. 844 85

1. In a previous investigation, Hoe 140, a specific and potent bradykinin B2 receptor antagonist, prevented the pancreatic oedema and the hypotension observed during acute experimental pancreatitis; however, it augmented the associated rises in the serum activities of pancreatic enzymes. Therefore, we have now investigated the consequences of the pancreatic oedema for the fate of activated enzymes released into the tissue during the course of acute pancreatitis. 2. Acute oedematous pancreatitis was induced in rats, pretreated with captopril (50 mumol kg-1, i.p.), by hyperstimulation of the exocrine function of the pancreas with the cholecystokinin analogue, caerulein (4 nmol kg-1 h-1, i.v.), for up to 120 min. 3. Pancreatic oedema began to develop 10 min after the start of the caerulein infusion, reached a maximum within about 45 min, and then declined slightly. The development of the oedema parallelled the second phase of the caerulein-induced fall in blood pressure found in earlier experiments. No further extravasation of plasma proteins occurred during the 2nd hour of the caerulein infusion. The oedema formation was completely blocked in animals pretreated with the bradykinin receptor antagonist, Hoe 140 (100 nmol kg-1, s.c.). Pretreatment with aprotinin or soy bean trypsin inhibitor did not result in a significant inhibition of the oedema. 4. The haematocrit of animals with experimental pancreatitis showed a pronounced increase which started 10 min after the start of the caerulein infusion and reached maximal values at 60 min. The changes in haematocrit showed a reduction in total blood volume of 28% due to a 48% loss of plasma. This effect was completely blocked by Hoe 140. 5. In rats with caerulein-induced pancreatitis, there was a time-dependent increase in the activities of amylase and lipase in blood serum as well as in the pancreas. Pretreatment with Hoe 140 greatly augmented the caerulein-induced rise in enzyme activities in blood serum but potently attenuated it in the pancreas. The activities of trypsin in both the blood serum and the pancreas were below or near the limit of detection in all experimental groups.6. It is concluded that the second phase of hypotension in this model of acute pancreatitis is due to the liberation of kinins which cause a massive loss of blood plasma into the pancreas and into the retroperitoneal space. Activated enzymes are trapped in the pancreas, at least in part, by the oedema of the gland. Treatment with Hoe 140 prevents the oedema formation and greatly facilitates the egress of activated enzymes from the pancreas.
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PMID:Pathological events in experimental acute pancreatitis prevented by the bradykinin antagonist, Hoe 140. 844 91

In order to approach impaired stimulus-secretion coupling in acute pancreatitis induced by a choline-deficient, ethionine-supplemented (CDE) diet in mice, the agonist-evoked intracellular Ca2+ dynamics of dispersed pancreatic acini were evaluated by microspectrofluorometry. Mice were fed a CDE diet for 24 or 48 h, and the pancreas was dispersed to the acini. The in vitro amylase secretion analysis of the CDE groups demonstrated a poor dose-response curve which was significantly lower (p < 0.01) when 100 pM cholecystokinin (CCK) was administered. Both in CDE and control groups, the application of a physiological dose of CCK-8 (10 pM) evoked intracellular Ca2+ oscillations. Periodicity and amplitude of the oscillations in the CDE groups were not significantly different. The administration of a higher dose of CCK-8 (100 pM) evoked a large, sharp, and transient rise in intracellular Ca2+, followed by a small, continuous increase above basal levels for the duration of stimulation both in CDE and control groups. The peak Ca2+ level was lower in the CDE groups, but this was not statistically significant. In conclusion, during the early phase (from 24 to 48 h) of CDE pancreatitis, the pattern of agonist-evoked intracellular Ca2+ release is less affected. Other mechanisms subsequent to the onset of intracellular Ca2+ release are likely to be involved in the inhibition of enzyme secretion.
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PMID:Intracellular Ca2+ dynamics and in vitro secretory response in acute pancreatitis induced by a choline-deficient, ethionine-supplemented diet in mice. 853 21

The role of cholecystokinin (CCK) in the development of a necrotizing acute pancreatitis induced by a diet deficient in choline and supplemented with ethionine (CDE) has been evaluated in the rat by using a potent CCK receptor antagonist L-364,718. Acute pancreatitis was induced by administration of CDE diet for 14 days. L-364,718 administration was carried out by subcutaneous injections at dose of 0.1 mg/kg/day. Pancreatic exocrine secretion (flow, protein, amylase and trypsin outputs) in resting and under infusion of 1.25 microgram/kg/h of CCK-8 were used to evaluate the pancreatic functionality. Others parameters (serum amylase, percentage fluid in pancreas, haematocrit and mortality) evaluated the severity of pancreatitis. L-364,718 slightly reduced the mortality and the increases of percentage of fluid accumulated in pancreas in CDE diet acute pancreatitis. Basal and CCK stimulated pancreatic secretion was significantly depressed 36 hours after L-364,718 treatment. A slight response to CCK was observed. Nevertheless it was lower than usually observed in control rats. Our results demonstrate that in the rat, chronic L-364,718 treatment did not completely restore pancreatic activity in acute pancreatitis induced by CDE diet. Hence CCK cannot be considered as the main factor involved in the development of this pancreatitis model.
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PMID:Effects of the cholecystokinin receptor antagonist L-364,718 on pancreatitis induced by a deficient in choline and supplemented with ethionine (CDE) diet in the rat. 854 74


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