Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:3.4.21.1 (chymotrypsin)
10,938 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Isolated pancreatic acini were prepared by a new method from mouse and rat pancreases by digestion with purified collagenase and chymotrypsin followed by mechanical shearing. Acini were structurally similar to those of the intact pancreas, having a normal luminal structure but with the basal acinar cell membranes exposed to the incubation medium. Amylase release in response to both cholinergic analogues and the cholecystokinin analogues caerulein and pentagastrin was comparable to that of the intact pancreas, but was much greater than previously reported for isolated acinar cells. Cholinergic-stimulated release was inhibited by atropine with a Ki value of 1.4 nM which is comparable to other muscarinic receptors. All agonists tested, when added at supramaximal concentrations, produced a submaximal release of amylase even though ATP levels and the release of slowly exchanging 45Ca2+ were normal or increased. Acini releasing amylase submaximally after being exposed to supramaximal concentrations of carbachol failed to respond to a maximal amount of caerulein or to the Ca2+ ionophore A23187. It is concluded that the decreased response (desensitization) is a postreceptor phenomenon and possibly mediated by Ca2+ itself.
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PMID:Action of secretagogues on a new preparation of functionally intact, isolated pancreatic acini. 21 42

Chronic administration of raw soybean flour containing active trypsin inhibitor to dogs reduced the pancreatic output of trypsin and chymotrypsin in response to cholecystokinin. Dogs stimulated by a meat meal showed no consistent alteration in the output of trypsin and chymotrypsin when given additional duodenal infusions of trypsin and chymotrypsin, or canine pancreatic juice, or ovalbumin trypsin inhibitor. Two dogs, whose pancreas was stimulated by intraduodenal infusion of amino acids, showed no consistent change when trypsin, or trypsin together with trypsin inhibitors, or trypsin together with canine pancreatic juice was infused concurrently into the duodenum. These results indicate that feedback control of pancreatic enzyme secretion, of the type proposed on the basis of studies similar to the present in rats, does not exist in dogs.
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PMID:Chronic and acute studies indicating absence of exocrine pancreatic feedback inhibition in dogs. 56 99

Fecal chymotrypsin (CT) activities were determined in 149 randomly collected fecal specimens of 80 patients in whom the pancreatic function had been tested by a secretin-cholecystokinin test. There was a significant correlation between fecal CT activities and outputs of trypsin (r = 0.3451, p less than 0.01) and amylase (r = 0.3285, p less than 0.01) in duodenal juice. Fecal CT activities were normal in all patients who--based upon enzyme outputs in duodenal juice after stimulation with secretin and CCK/PZ--were classified as 'borderline cases', in most patients with 'low-normal' pancreatic function, and in a significant number of patients with established insufficiency of exocrine pancreas. On the other hand, fecal CT activities were abnormal in patients with severely impaired output of trypsin in duodenal juice, and only 7% of the fecal specimens from patients with established normal function of exocrine pancreas had abnormal low CT activities. It is concluded that the sensitivity of the fecal enzyme method is rather low as compared to the secretin-cholecystokinin test, but that fecal CT determinations give valuable diagnostic information in patients with more pronounced insufficiency of the exocrine pancreas.
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PMID:Fecal chymotroypsin: a study on its diagnostic value by comparison with the secretin-cholecystokinin test. 68 Apr 17

Duodenal juice was collected from 50 healthy patients in the basal state, and after intravenous injection of 1 clinical unit of secretin kg-1 + 3 Crick-Harper-Raper units of cholecystokinin-pancreozymin (CCK-PZ) kg-1. Amylase to chymotrypsin and amylase to lipase ratios were significantly decreased by stimulation. Pure pancreatic juice was collected from 7 healthy subjects by endoscopic retrograde catheterization of the papilla. Secretin (1 clinical unit kg-1 hr-1) was infused intravenously during 30 min, and a single intravenous injection of CCK-PZ (3 Crick-Harper-Raper units kg-1) was done at the 15th min of the secretin infusion. Chymotrypsinogen and lipase secretions did not parallel that of amylase during CCK-PZ stimulation. As in the first set of experiments, amylase secretion was proportionally less stimulated by CCK-PZ injection than were chymotrypsinogen and lipase secretions. However, in approximately 20% of subjects the secretion of the enzymes was parallel in both duodenal and pancreatic juice.
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PMID:Nonparallel secretion of enzymes in human duodenal juice and pure pancreatic juice collected by endoscopic retrograde catheterization of the papilla. 86 99

Pancreatic secretory abnormalities develop in most persons with pancreatic cancer and have been attributed to ductal obstruction. These experiments investigated whether abnormal secretion results instead from carcinogen-induced changes in the secreting cells. Fifty male Syrian Golden hamsters (40 to 100 grams) received weekly injections of di-isopropyl-nitrosamine (250 mg/kg, subcutaneously), and survivors and age-matched controls were studied after 3.5 to 6.5 months of treatment. Pancreatic secretion was stimulated by secretin or cholecystokinin (2 units/kg, intravenously, as a bolus). After each stimulus four 15-minute collections of pancreatic juice were analyzed for HCO3- and Cl- or total protein, amylase, trypsin, and chymotrypsin. The organs were examined histologically. Pancreatic ductal adenocarcinoma developed in 30% of the animals at 5 months, 56% at 5.5 months, and 100% at 6.5 months. The animals without cancer either had hyperplasia of the duct epithelium or were histologically normal. The histologic appearance of acinar tissue and protein secretion were normal in all groups. The tumors did not obstruct the major ducts. In all treated animals the pancreatic secretory response to secretin was of low volume, low maximal [HCO3-] and HCO3- output, and low [Cl- + HCO3-]; these changes progressed with time. The secretory abnormalities antedated the appearance of the neoplasms and were not caused by obstruction.
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PMID:Pancreatic secretion in hamsters with pancreatic cancer. 87 54

Secretion of trypsin, chymotrypsin, lipase and amylase was measured in male rats under urethane anaesthesia using a method of continuous perfusion of the duodenum. Prolonged infusion of cholecystokinin-pancreozymin (CCK-PZ) over a period lasting 200-360 min was administered either alone or together with a submaximal dose of secretin (1 unit/100 g - 10 min). Infusion of CCK-PZ was carried out using maximal doses (1--1.5 unit/100 g - 10 min) with and without secretin. Supramaximal doses of CCK-PZ (2 and 4 units/100 g - 10 min) were used only in combination with secretin. In all experiments secretion of enzymes showed a triphasic pattern including an initial peak followed by a plateau secretion after 10--20 min (phase 1), a decreasing second phase and finally base-line secretion (phase 3), thus demonstrating exhaustion of enzyme output from the gland with time. With increasing and supramaximal dose of CCK-PZ the cumulative output of enzymes from start to baseline secretion decreased progressively. Under the same conditions the levels of peak and plateau secretion were lower, the duration of plateau secretion was longer and the decreasing phase of secretion was shortened. These features indicate inhibition of secretion with increasing supramaximal doses of CCK-PZ infusion. Whereas the proteolytic enzymes and lipase reacted in a parallel way always amylase secretion was sustained on a higher level, implicating an alternative pathway for secretion.
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PMID:Effect of prolonged infusion of maximal and supramaximal doses of pancreozymin on pancreatic enzyme secretion in the rat--exhaustion or inhibition? 94 24

The exocrine pancreatic function was studied in humans by performing a secretin-cholecystokinin test before and after treatment with oxytetracycline or chloramphenicol. In the oxytetracycline-treated patients there was a depression of the amylase and lipase outputs in the duodenal secretion, chymotrypsin decreasing only slightly. After treatment with the two antibiotics the calcium secretion was reduced. The other parameters measured in the duodenal secretion remained essentially unchanged. The enzyme dissociation observed in the present studies is considered to reflect the onset of pancreatic dysfunction due to antibiotic administration. As in the previous animal onset of pancreatic dysfunction due to antibiotic administration. As in the previous animal experiments, the suggested explanation for the changes in enzyme secretion is an inhibition of protein synthesis in the exocrine pancreas due to oxytetracycline and chloramphenicol.
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PMID:Exocrine pancreatic function in man after treatment with oxytetracycline and chloramphenicol. 95 76

The role of exogenous and endogenous cholecystokinin has been studied in the process of pancreatic regeneration after acute pancreatitis. A mild form of pancreatitis was induced in rats by subcutaneous cerulein at 12 micrograms.kg-1, three times a day for 2 days. After 3 days of rest, the cerulein-treated rats were divided into four groups: rats with acute pancreatitis fed 20% casein, who received no treatment; rats fed 50% casein; rats fed 20% casein supplemented with 1% soybean trypsin inhibitor (SBTI); and rats fed 20% casein who received 1 microgram.kg-1 of subcutaneous cerulein, three times a day. Controls were fed 20% casein plus saline subcutaneously. Rats were killed after 5, 10, or 20 days of treatment. Pancreatitis resulted in significant decreases in pancreatic weight and contents of protein, amylase, chymotrypsin, RNA and DNA. During the regenerative process, 1 microgram.kg-1 of cerulein increased all parameters to control values within 5 days and induced pancreatic growth thereafter. SBTI restored the pancreas to normal after 10 days with cellular hypertrophy; the 50% casein diet gave a response similar to SBTI without hypertrophy. It can be concluded that cerulein and SBTI can accelerate pancreatic regeneration after an attack of acute pancreatitis.
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PMID:Soybean trypsin inhibitor and cerulein accelerate recovery of cerulein-induced pancreatitis in rats. 137 Jun 63

We examined the effects of bombesin on rat pancreatic digestive enzyme gene expression using cloned complementary DNA probes for amylase, trypsinogen I, chymotrypsinogen B, and lysophospholipase. Rats were injected sc three times daily with 5 nmol/kg body wt bombesin. Pancreata were investigated after 6, 12, 24, 48, and 120 h of hormone treatment. Bombesin administration resulted in a time-dependent increase of pancreatic weight, as well as DNA and protein concentration. Cellular hypertrophy became evident after 48 h, and pancreatic hyperplasia occurred after 5 days of hormone treatment. Bombesin administration resulted in a time-dependent parallel decrease of amylase and lysophospholipase messenger RNA (mRNA) concentrations with maximal inhibition occurring after 120 h of bombesin treatment (13 +/- 1% and 14 +/- 3% of control, respectively, P less than 0.05, n = 6). In contrast, chymotrypsin and trypsin mRNA levels remained unaltered after bombesin treatment for up to 5 days. Amylase and chymotrypsin enzyme levels did not correlate with their respective mRNA concentrations. Both decreased to approximately 50% of control after 12 h and increased to 126 +/- 38% of control and 388 +/- 109% of control (P less than 0.05, n = 6), respectively, after 5 days of bombesin treatment. To test whether the bombesin regulation was mediated by the release of cholecystokinin (CCK), the specific CCK receptor antagonist L-364,718 (1 mg/kg body wt) was injected ip either alone, or 15 min before each bombesin injection for 5 days. Although the antagonist alone significantly reduced the mRNA concentrations for trypsin, chymotrypsin, and lysophospholipase to approximately 50%, it did not block the effects of bombesin on pancreatic digestive enzyme levels. These data therefore indicate that bombesin regulates pancreatic digestive enzyme mRNA and protein concentrations in a nonparallel manner; furthermore, CCK is not involved in mediating the bombesin effects on pancreatic gene expression.
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PMID:Effects of bombesin on pancreatic digestive enzyme gene expression. 137 50

The role of cholecystokinin (CCK) in induction and maintenance of pancreatic growth stimulated by a high-protein diet was investigated. Rats adapted to 5% casein diet were switched to 70% casein for 21 days. MK-329, a CCK receptor antagonist, was administered at 2.5 mg.kg-1.day-1 ip, beginning on day zero (day zero treatment) or day 7 (midcourse treatment) of feeding 70% casein and thereafter. Another group was returned to 5% casein after 7 days of feeding 70% casein. Feeding 70% casein significantly stimulated increases of 32, 87, 74, 216, and 1,450% in pancreatic DNA, RNA, wet weight, protein content, and chymotrypsin content, respectively. Midcourse treatment with MK-329 was more effective than day zero treatment, and it completely reversed increases in pancreatic weight and RNA content, partially reversed increases in protein and chymotrypsin content, and had no effect on DNA content. Return to 5% casein rapidly reversed increases in pancreatic parameters, except for DNA. The results indicate that CCK is essential for induction and maintenance of dietary protein-stimulated pancreatic hypertrophy.
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PMID:Role of cholecystokinin in induction and maintenance of dietary protein-stimulated pancreatic growth. 137 68


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