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

1. Intestinal brush border enzymes have heterogeneous rates of turnover, the largest proteins having the fastest turnover. Since the membrane faces the intestinal lumen, the effects of pancreatic factors were examined in mediating this turnover. Surgical subtotal pancreatectomy was used as an experimental model to study the turnover of brush border proteins in the absence of most pancreatic secretions. 2. Subtotal (95%) pancreatectomy of rats was found to cause elevations by about 50% of total activity and specific activities of certain brush border enzymes (maltase, sucrase, lactase), but not of others (alkaline phosphatase, trehalase). Rats were judged to be functionally deficient in pancreatic proteolytic enzymes (a) by demonstration of vitamin B-12 malabsorption, which was corrected by trypsin, and (b) by the finding of only about 20% of proteolytic activity appearing in the lumen after a test meal when compared to control. 3. To measure protein turnover in vivo the method of double labelling was used, where [3H]- and [14C]valine were administered intraduodenally in sequence 10 h apart. With this technique, a high 3H/14C ratio is correlated with rapid turnover. Proteins with apparent molecular weights of about 200 000-270 000 were found to turn over more rapidly than smaller proteins. 3H/14C ranged from 4.7 to 6.2 in animals without pancreatic insufficiency. In the face of decreased pancreatic proteolysis, the 3H/14C ratio was 2.3-3.1, similar to that of proteins with a slow half life. 4. Estimates of relative synthetic rates of large brush border proteins were lower than normal in pancreatectomized animals, but were constant over the period of the labelling experiment. The high enzyme levels in the face of lower synthetic rates confirms that, at the new steady rate, degradation rates must be slower for large brush border proteins in pancreatic insufficiency. 5. In vitro, using purified brush borders, unfractionated pancreatic enzymes were found to remove sucrase, maltase and lactase, but not alkaline phosphatase and trehalase. The enzyme most potent in this respect was the pancreatic protease, elastase. Non-proteolytic enzymes (amylase, lipase, phospholipase A) were inactive in removing enzyme from the brush border. The addition of elastase to pancreatectomized animals in vivo restored the rapid turnover rate of large brush border proteins. 6. A model is thus proposed for the normal catabolism of some large intestinal brush border proteins. It is suggested that the surface of intestinal absorptive cells is being constantly remodelled, and that certain surface enzymes are in part removed from the membrane by the action of pancreatic proteases. A possible special role for elastase is suggested.
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PMID:The possible role of pancreatic proteases in the turnover of intestinal brush border proteins. 114 88

1. A method for collecting duodenal juice and gastric content separately, in conscious rats, is described. Metal cannulas were implanted into the stomach fundus. For the main experiment a double lumen tube was inserted through the cannula via the pylorus into the duodenum. 2. The following secretion patterns were observed: a) In the resting state there was a constant flow rate of duodenal volume, bicarbonate, trypsin and amylase. b) Cholinergic stimuli were capable of increasing enzyme secretion as much as fourfold for a period of 30 to 40 min when administered as a single subcutaneous injection. This effect was annulled by atropine. c) Secretin and cholecystokinin-pancreozymin given together in a single injection s.c. or i.v., elicited a similarly strong response. d) Identical ranges of the secretion maxima were found with a tendency to decrease after the first hour, when the hormones were infused either s.c. or i.v. e) Doses from 0.5 to 25 U/100 g b.w. /hr showed identical responses. Doses below 0.2 U/100 g/hr were without effect. 3. Narcosis (pentobarbital) inhibited markedly the resting and stimulated enzyme secretion. 4. The method is suitable for examination of physiological and pharmacological effects on resting and stimulated enzyme secretion of the rat pancreas.
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PMID:Pancreatic enzyme secretion in the conscious rat. Method and application. 116 69

Elastolytic activity of human duodenal contents was determined using the new chromogenic substrate succinyl-trialanine-p-nitroanilide (Suc-Ala3-NAp). The mean output values after pancreatic stimulation with pancreozymin and secretin were significantly higher in controls than in subjects with impairment of other secretory values (volume, bicarbonate, amylase, lipase). Agar gel electrophoresis and chromatography on DEAE-Sephadex revealed one to two fractions which differed in mobility (cathodic and anodic fraction), elution with different NaCl concentrations (0.15 M, cathodic fraction; 0.3 M, anodic fraction), and in behaviour towards synthetic and natural substrate (Suc-Ala3-NAp) and elastin-Congo Red). The cathodic fraction cleaved both substrates, whereas the anodic fraction cleaved only Suc-Ala3-NAp. After trypsin and enterokinase treatment the anodic fraction behaved as the cathodic fraction on DEAE-Sephadex chromatography. The molecular weights (Sephadex G-100) and the Michaelis constants (Suc-Ala3-NAp) of both fractions were identical (24 500; 0.45 X 10(-3) M). These fractions represent probably diffenent activation forms of pancreatic elastase.
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PMID:Elastolytic activity of human duodenal contents. 117 3

In 14 normal individuals and in 28 patients with chronic recurrent pancreatitis the total secretion of amylase, lipase and trypsin, as well as the proportions of these enzymes in 20 minute portions of the duodenal contents under basal conditions and after an intravenous injection of 1.5 Un/kg of the "Boots" pancreozymin were studied. A definite disproportion in the stimulated secretion of pancreatic enzymes with a higher amylase/lipase ratio and a lower lipase/trypsin ratio was found to occur as a physiological phenomenon, the degree of this disproportionality, however, being substantially greater in patients with chronic pancreatitis than in healthy persons. An inference is drawn that, along with an investigation into the overall amount of enzymes secreted secondary to pancreozymin stimulation, of importance is not so much the very fact of divulging the non-proportionality of the stimulated pancreatic enzymes secretion, but rather the analysis of the nature and the degree of this disproportionality. This is essential, in particular, when estimating the effect of various nutritional patterns on the external secretion of the pancreas.
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PMID:[Analysis by means of pancreatozymin of the degree of parallelism of secretion of pancreatic enzymes in healthy persons and patients with chronic pancreatitis]. 119 10

Within a few hours after one injection of fresh human serum by the intraperitoneal route only, mice developed pancreatic acinar cell necrosis and inflammation, fat necrosis, elevated serum amylase and a shocklike state. The extent of these lesions and mortalities were roughly dose dependent and were not noticeably modified by either different fasting cycles or pilocarpine. Acinar cell changes and necrosis usually developed first in subserosal acini. The earliest ultrastructural change detected was nonspecific swelling of cytoplasmic compartments which was reversible but also preceded the cytoplasmic degradation that developed in cells undergoing necrosis. Notably, zymogen granule dissolution neither preceded nor accompanied this swelling, but developed pari passu with cell degradation. Occasionally, intact granules were found in necrotic cells. Serum was cytotoxic for isolated acinar cells in vitro, even in the presence of soybean trypsin inhibitor. These results (1) indicate that the injury mechanism in vivo is directly initiated through contact of serum with acinar cell surfaces and is independent of zymogen secretions and trypsin activation, and (2) suggest that a rapid disturbance in cell membrane permeability results, the magnitude of which being the primary determinant of cell death. Pancreatic toxicity of human serum was abolished by aging, heating, ethylenediaminetetraacetic acid, heparin, zymosan, cobra venom factor, and absorptions with mouse red blood cells, against which fresh, unabsorbed serum was hemolytic. Pancreatic toxicity in vitro and, to a much lesser extent, in vivo was reconstituted by combining the red blood cell-absorbed serum with either heated serum, or with IgM-enriched, but not IgG serum fractions. Fresh cord serum was virtually nontoxic and could substitute for absorbed serum in such reconstitutions. These results indicate that the injury mechanism involves at least two serum components. By both circumstance and analogy, other results and a review of other examples of foreign sera toxicity suggest that they are components of a complement-dependent, cytotoxic heterophile antibody system. The relevance of this odd phenomenon is that it offers a simple model of acute pancreatitis, contributes to the debunking of traditional notions of the pivotal role of zymogens in the initiation of acute pancreatitis, and hints at a potential pathogenetic connection between pancreatitis and products of immune or related reactions.
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PMID:Foreign serum-induced pancreatitis in mice. I. A new model of acute pancreatitis. 120 81

Using the secretin-pancreozymin test, the function of the exocrine pancreas was studied in patients with malignant disease before and after massive-dose therapy with cyclophosphamide and before and after combined cytotoxic treatment (as outlined by De Vita). The investigations further included an examination of the exocrine pancreatic function in subjects on maintenance therapy with clyclophosphamide of Myleran and a comparison with the exocrine pancreatic function in a group of controls. In the patients on massive-dose or continued therapy with cyclophosphamide the volume of the duodenal secretion and the bicarbonate, electrolyte and enzyme outputs in the duodenal secretion remained essentially unchanged. In contrast, cytotoxic combination treatment resulted in decreased activities of amylase and lipase, and in some cases of trypsin. After maintenance treatment with Myleran a reduction of the trypsin and amylase activities was detectable; chymotrypsin and lipase were found to be slighthly lowered.
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PMID:Exocrine pancreatic function in man after cytotoxic treatment. 121 Oct 65

The effect of different food substrates on production by the duodenal mucosa of factors acting on the endocrine and exocrine functions of the pancreas was studied in the rat in vivo. Intragastric loads of glucose, maltose, arginine, lysine, peanut oil or a protein hydrolysate (Nesmida) were given to a first group of rats. The duodenum was removed at various times after food and extracts of duodenal mucosa were injected into the pancreatic-duodenal artery of other rats. The effect of these extracts was determined by measuring immunoreactive insulin levels in the portal vein and amylase, trypsin and lipase activities in the pancreatic juice of this second series of rats. Glucose and arginine, but not lysine, increased the activity of duodenal extracts on insulin secretion, whereas oil ingestion modified the activity of the duodenal extracts by inhibiting insulin secretion. Duodenal mucosa extracts taken 30 min after glucose and maltose ingestion stimulated amylase but not trypsin in the pancreatic juice, whereas extracts taken 45 min after ingestion of a protein hydrolysate stimulated trypsin but not amylase production. The extracts taken after oil ingestion specifically stimulated lipase secretion. These observations suggest the possibility of a hormonal system which is modulated by various food substrates and influences both endocrine and exocrine pancreas functions.
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PMID:[Dietary modification of a specific hormonal system of the duodenal mucosa controlling the endocrine and exocrine pancreatic secretions]. 121 58

The effect of bombesin on external pancreatic secretion was studied in seven healthy volunteers and intwo patients with a two-thirds gastrectomy and a pancreatic fistula. After bombesin infusion (15 ng/kg/min), gastrin levels were significantly raised in all volunteers, but remained at basal levels in the gastrectomized patients. Bombesin was effective in stimulating pancreatic secretion in all patients. The volume of secretion increased tow-fold when compared with basal volume. Amylase and trypsin concentrations and outputs in the duodenal juice were greatly agumented (amylase concentration: basal, 70 dye U/ml; post-bombesin, 620 dye U/ml. Amylase output: basal, 1000 dye U/15 min; post-bombesin, 15,800 dye U/15 min). Secretin, when administered in conjunction with bombesin, partially inhibited its secretory effect. Bicarbonate secretion was slightly stimulated by bombesin, but at a very low level. A similar pattern of results was obtained in the two gastrectomized patients. In man, bombesin exerts an effect on pancreatic secretion that mimics the effect of CCK-PZ, thus confirming the results obtained in the experimental animal. Gastrin does not play a fundamental role in this phenomenon.
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PMID:External pancreatic secretion after bombesin infusion in man. 121 23

Abnormal responses of plasma lipase, trypsin, and amylase to pancreozymin and secretin in poorly controlled diabetics were found in 42%, 41% and 30% while these responses in well controlled diabetics were 25%, 9% and 9% respectively. Positive provocation of at least one of these enzymes was observed in 67% of poorly controlled diabetics and was significantly more frequent than that (18%) in well controlled diabetics (p less than 0.01). An elevation of fasting lipase and amylase activities was also noted in 26% and 37% in the former in contrast to 0% and 18% in the latter. In the same 6 subjects the degree of abnormal plasma enzyme response was greater in the poorly controlled diabetic state than in the well controlled diabetic state. When insulin effect on plasma lipase response was tested in experimentally diabetic rats, insulin administration for 3 to 5 days normalized the abnormal provocation of lipase observed in chronically diabetic rats. These findings indicate that pancreatic enzymes tend to leak to the systemic circulation in insulin deficiency.
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PMID:A high incidence of positive provocation of plasma pancreatic enzymes in the poorly controlled diabetic subjects. 122 2

A comparative enzyme analysis was performed on 3 pancreatic extracts generally used for dermal-epidermal separation, namely, crude trypsin (Difco), crude trypsin (Sigma) and pancreatin. A fourth pancreatic extract, crude lipase, was subjected to a corresponding analysis. The 4 extracts were assayed for activities of: protease (total), trypsin, chymotrypsin, carboxypeptidase-A, amylase, elastase, lipase, esterase, arylesterase and ribonuclease. Relative activities of the different proteolytic enzymes were individualized by utilizing specific inhibitors. Insignificant differences were observed between the enzyme activities of crude trypsin (Difco) and pancreatin. Crude lipase displayed similar enzyme activities as these two extracts in addition to high lipolytic, esterolytic and arylesterolytic activities. Crude trypsin (Sigma) exhibited higher tryptic and chymotryptic activities than the other extracts but lacked all further enzyme activities. Epidermal separation was performed using similar incubation conditions for each extract and skin from the same donor. Ultrastructural examination of the detached epidermis revealed that a more effective separation could be achieved by crude lipase.
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PMID:An analysis of pancreatic enzymes used in epidermal separation. 123 61


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