Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.4 (trypsin)
 42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Pancreatic insufficiency was induced in rats by a single injection of 50 microliter oleic acid into the pancreatic duct over a period of 3 min. Exocrine tissue was destroyed within 3-6 days, and after 6 weeks the remaining pancreas equaled 2.7% of the original organ. The rats showed retardation of body weight in spite of normal food intake. After 7 weeks the fecal weight increased by 23%, and the fecal chymotrypsin activity decreased by 90% compared to controls. At this time plasma cholecystokinin (CCK) concentrations were significantly elevated. The amylase content in the remaining pancreas was reduced by 99%, and trypsin content was reduced by 93%. Unstimulated protein discharge from the remnant pancreas in vitro was threefold higher compared to secretion from control tissue. Thus a simple, reproducible model for inducing persistent pancreatic insufficiency was developed. To compensate for the loss of exocrine tissue, the remaining acinar cells adapt by a CCK-mediated increase in protein secretion.
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PMID:Exocrine pancreatic function in oleic acid-induced pancreatic insufficiency in rats. 243 60

The acute and chronic effects of hydrocortisone on exocrine pancreatic function were examined in the isolated perfused rat pancreas. In the first part of this study, rats were given subcutaneous injections of hydrocortisone at doses of 1.25, 2.5, 5, and 10 mg/kg body wt once daily for 7 days. Trypsin and lipase secretion in response to 100 pM cholecystokinin-octapeptide was significantly increased in rats with the two highest doses of hydrocortisone compared with controls, irrespective of whether calculated as the total amount of stimulated output of enzymes or related to the secretion of enzyme to the pancreas content. On the other hand, the secretory responsiveness of amylase to 100 pM cholecystokinin-octapeptide was maximal at the 5-mg dose, and decreased with higher doses. In the second part, 100 microM hydrocortisone was superimposed for 20 min on 100 pM cholecystokinin-octapeptide stimulation to examine the acute effects of hydrocortisone on exocrine pancreatic function in the isolated perfused rat pancreas. Addition of hydrocortisone caused a significant inhibition of the secretion of pancreatic juice and amylase. The present study has clearly demonstrated the dual effects of glucocorticoids on the pancreas: inhibition and potentiation. There is a possibility that chronic treatment with large doses of glucocorticoid may sensitize the acinar cells an induce hypersecretion of trypsin and lipase, whereas acute treatment inhibits secretory function of exocrine pancreas.
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PMID:Dual effects of hydrocortisone on exocrine rat pancreas. 244 19

This study was performed to investigate adaptive changes of the exocrine pancreas occurring after distal gastric resection by different procedures: Billroth I (BI) and Billroth II (BII). Sixty-four male Wistar rats were used and divided into four groups: controls (n = 16), sham-operated (n = 16), BI (n = 16) and BII (n = 16) subtotal gastric resection. Both procedures of subtotal gastric resection showed an organotrophic effect on the pancreas after 2 weeks: pancreatic weight in BI- and BII-operated rats increased by 23 and 35% and DNA content by 36 and 27%, respectively, compared to controls (p less than 0.001). After 4 weeks a further increase in pancreatic weight (46%), DNA content (52%) and protein content (58%) was found in BII rats. Trypsin and amylase content were increased in BI rats after 2 weeks (p less than 0.01). No parallel changes were observed in the enzyme content of BII rats as trypsin increased by over 200%, amylase by over 100% and lipase remained unaffected. Hormonal studies were carried out in 36 rats divided into groups as above. Basal and stimulated plasma levels of gastrin were reduced (p less than 0.01) following both types of subtotal gastric resection (p less than 0.01). Basal cholecystokinin (CCK) plasma levels did not differ between operated and control rats. Following the test meal CCK plasma levels were significantly increased after BII gastric resection (p less than 0.001) and BI gastric resection (p less than 0.01) compared to controls.
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PMID:Adaptive changes of the exocrine pancreas and plasma cholecystokinin release following subtotal gastric resection in rats. 245 Jul 98

The mechanisms of pancreatic adaptation to dietary changes and whether these changes are reflected in the serum are not fully understood. The present study investigates secretagogue-induced release of digestive enzymes from dispersed pancreatic acini as well as the concentrations of these enzymes in serum and pancreas after adaptation to a high protein diet. Adult rats were fed an 8.5% casein diet ad libitum. After 14 d the rats were divided into three groups and fed isoenergetic diets constituting 8.5, 24 or 40% protein for an additional 6 d. No significant differences in final body weight or pancreatic weight were observed among the groups of rats. Rats adapted to the 40% protein diet showed significantly higher trypsin and chymotrypsin activity in pancreatic homogenates than rats fed the 8.5% protein diet. These changes in pancreatic enzyme content were not reflected in serum. Pancreatic acini isolated from the 8.5% protein group showed a markedly reduced responsiveness to cholecystokinin (CCK-8), secretin- and carbachol-induced enzyme release in comparison to the other two dietary groups, although basal enzyme release was the same in all groups. These results indicate that the secretion of pancreatic enzymes following a physiological stimulus is affected by a low protein, high carbohydrate diet.
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PMID:Secretagogue-induced enzyme release from the exocrine pancreas of rats following adaptation to a high protein diet. 245 Sep 76

This study describes the effect on the function and structure of the saline-perfused cat pancreas of factors implicated in the pathogenesis of pancreatitis (bile acid, ethanol, pancreatic enzymes) after their addition to the perfusion fluid or their instillation into the pancreatic duct. Instillation of trypsin or chenodeoxycholic acid, but not ethanol, into the pancreatic duct resulted in a profound suppression of secretory function. The leakage of perfusion fluid and amylase from the gland was also abruptly increased. Intraarterial perfusion of trypsin also inhibited secretin-induced flow and cholecystokinin evoked enzyme secretion. Intraarterial bile acid inhibited fluid flow but augmented enzyme secretion in a concentration-dependent manner. In addition, massive or focal parenchymal necrosis was caused by sustained intraarterial perfusion of bile acid or trypsin, respectively. Elastase and phospholipase A had little influence on pancreatic function or structure when added to the perfusion fluid. These findings show that pancreatic structure and function can be disturbed by potentially toxic factors administered not only via the ductal system but also via the vascular route, and consequently suggest that an "internal reflux" mechanism could be involved in the pathogenesis of pancreatitis in addition to a "ductal reflux" mechanism.
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PMID:Analysis in the isolated perfused cat pancreas of factors implicated in the pathogenesis of pancreatitis. 245 94

To determine if human lipase is inactivated by trypsin and chymotrypsin, we intubated 22 human subjects with an oroduodenal tube and stimulated pancreatic secretion with cholecystokinin octapeptide. The duodenal aspirate from each subject was divided into a control and a test sample and incubated in a 37 degrees C water bath for 2 h. An inhibitor of trypsin or chymotrypsin or more of one of these enzymes was added to the test sample. We found that the loss of lipase activity was partly prevented by inhibiting trypsin with aprotinin (910 KU/ml; P = 0.03) and was accelerated by adding bovine trypsin (2.5 mg/ml; P = 0.01). Inhibiting chymotrypsin with turkey egg white (2.5 mg/ml) totally abolished the loss of lipase activity (P = 0.01), and addition of bovine chymotrypsin (5 mg/ml) accelerated the loss of lipase activity more than adding trypsin (P = 0.01). After inhibiting chymotrypsin (to maintain lipase activity), increasing trypsin activity by adding a single or repeated doses of trypsin did not decrease lipase activity. Conversely, the addition of a single dose of chymotrypsin after inhibiting trypsin activity markedly decreased lipase activity (P less than 0.004). In conclusion, chymotrypsin is a more potent inactivator of human lipase than trypsin; chymotrypsin inactivates lipase in the absence of trypsin, but trypsin inactivation of lipase requires chymotrypsin.
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PMID:Inactivation of human lipase by proteases. 245 71

Diversion of bile pancreatic juice from the duodenum in rats stimulates cholecystokinin (CCK) release and pancreatic enzyme secretion. Intraduodenal perfusion of trypsin inhibits the release of CCK and pancreatic enzyme secretion. We hypothesized that the increased pancreatic enzyme secretion after pancreatic juice diversion is mediated by a trypsin-sensitive peptide secreted by the small intestine that stimulates release of CCK. To test this hypothesis, rats were surgically prepared with bile-pancreatic cannula and intestinal fistulas. Diversion of bile-pancreatic juice stimulated amylase output fivefold above basal and increased plasma CCK from a basal of 0.5 +/- 0.05 pM to 14 +/- 5 pM. Rapid perfusion (3 ml/min) of the duodenum with phosphate-buffered saline reversed the increase in amylase output and lowered the plasma CCK to 1.2 +/- 0.2. Administration of intestinal perfusate (3 ml/min) collected from a donor rat into the duodenum of a recipient rat with diversion of bile pancreatic juice increased amylase output threefold above basal and increased plasma CCK. The stimulatory activity of the intestinal perfusate was inactivated by treatment with trypsin but not by amylase or lipase. In addition, boiling did not alter the stimulatory activity of the intestinal perfusate. Perfusion of intestinal perfusate from donor rats pretreated with atropine did not stimulate amylase output and CCK release in recipient rats. By use of molecular membrane exclusion filters, stimulatory activity was retained (between 1,000 and 5,000). These results indicate that feedback regulation of pancreatic enzyme secretion is mediated by a CCK releasing peptide whose secretion from the duodenum is cholinergically mediated. This peptide is trypsin sensitive and has a molecular weight between 1,000 and 5,000.
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PMID:A cholecystokinin releasing peptide mediates feedback regulation of pancreatic secretion. 246 98

1. The effect of lorglumide, a new potent cholecystokinin (CCK) antagonist, on pancreatic secretion and growth induced by caerulein and bombesin was studied in the rat. 2. Pancreatic exocrine secretion was studied both in vitro (isolated and perfused pancreatic segments) and in vivo (anaesthetized animals with cannulation of the common bile duct) whereas the trophic effect was investigated after short-term (5 days) administration of the peptides and/or lorglumide. 3. Both caerulein and bombesin stimulated amylase release from in vitro pancreatic segments in a concentration-dependent manner. Although the efficacy of both peptides was virtually identical, the potency of caerulein was higher than that of bombesin. Lorglumide displaced the concentration-response curves to caerulein to the right without affecting the maximum response, suggesting a competitive antagonism. The Schild plot analysis of data gave a straight line with a slope not significantly different from unity. The calculated pA2 for lorglumide was 7.31 +/- 0.45. The antagonist, however, was completely ineffective when tested against bombesin-induced amylase release. 4. In vivo experiments confirmed results from in vitro studies since lorglumide (5 and 10 mg kg-1) significantly reduced pancreatic exocrine secretion induced by caerulein without affecting the response to bombesin. 5. Administration of either peptide increased the weight of the pancreas, the total pancreatic protein and DNA, trypsin and amylase content. Lorglumide (10 mg kg-1), administered together with caerulein, reduced the peptide-induced increase in pancreatic weight, protein and enzyme content. On the contrary, when lorglumide was given together with bombesin, all the parameters that were examined were not altered by concomitant administration of the antagonist. 6. These results have demonstrated the ability of lorglumide to antagonize the effects on the pancreas of a CCK-analogue, caerulein, and its inability to affect bombesin-induced pancreatic secretion and growth, suggesting that lorglumide is a potent and selective antagonist of CCK-receptors in the pancreas.
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PMID:Effect of a new potent CCK antagonist, lorglumide, on caerulein- and bombesin-induced pancreatic secretion and growth in the rat. 247 Apr 56

Influence of alcohol administration on the trophic effect of cholecystokinin-octapeptide and soybean trypsin inhibitor administration was examined in male Wistar rats. Two x 4 mL of 20% alcohol given intragastrically during 2 wk did not significantly influence pancreatic weight, DNA, protein, trypsin, chymotrypsin, amylase, lipase, or trypsin inhibitor contents of the pancreas. It diminished the hypertrophy but not the hyperplasia seen after CCK-8 treatment, and eliminated the hyperplasia, as well as the hypertrophy provoked by SBTI administration. Secretory studies and CCK measurements demonstrated decreased CCK release in response to SBTI stimulation after 3-d alcohol administration. The results indicate that alcohol inhibits the enzyme synthesis of the CCK stimulated dividing and/or newly formed acinar cells and the endogenous CCK release.
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PMID:Mechanisms of action of alcohol administration on the trophic effect of soybean trypsin inhibitor and cholecystokinin octapeptide in rat. 247 19

We have studied the reliability of serum and urinary immunoreactive anionic trypsin (irAT), immunoreactive cationic trypsin (irCT), and amylase activity as rejection indicators in a porcine whole-organ pancreaticoduodenal transplantation model with exocrine drainage to the urinary bladder. No immunosuppressive therapy was administered. Exocrine tissue integrity and function were studied by measuring these enzymes in serum and urine. Urine analyses were performed before and after an intravenous secretin-cholecystokinin stimulation. Of 16 transplanted pigs, 10 became diabetic during a 2-week observation period while six remained normoglycemic. Serum irAT was found to predict rejection while serum amylase and serum irCT did not. An increase in irAT was seen in rejecting pigs preceding the onset of hyperglycemia by a median of 2 days (range 1-9). Secretion of irAT into the urine remained high during the observation period in nondiabetic pigs while the output declined in diabetic pigs. This decline was seen after the increase in serum irAT. When urine was sampled after a secretin-CCK stimulation, these findings were clearly evident, but less unequivocal results were obtained without stimulation. IrAT measurements were superior to measurements of amylase, irCT, or bicarbonate. Thus rejection of a pancreatic allograft was first indicated by a temporary rise in serum immunoreactive anionic trypsin, probably due to the onset of tissue damage. Thereafter, stimulated urinary enzyme output levels gradually declined and finally, hyperglycemia developed.
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PMID:Pancreatic enzymes in serum and urine as indicators of pancreatic allograft rejection in the pig. 247 76


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