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)

In rats, treated chronically with saline and nicotine, we studied the postprandial release of gastrin and cholecystokinin by specific radioimmunoassays and simultaneously measured secretory outputs of the exocrine pancreas. Rats were prepared surgically with gastric and pancreatic fistulas. Meal-stimulated release of peptides and exocrine secretory outputs were measured 24 h postoperatively in conscious rats. Infusion of food via intragastric cannula significantly stimulated plasma gastrin levels in both control and nicotine treated rats. Postprandial gastrin levels in nicotine treated rats were significantly higher compared to gastrin levels obtained after food in untreated control rats. Plasma CCK levels were increased in both groups after food. These levels remained significantly elevated from the basal values only for a transient period following infusion of the liquid meal. There were no differences in postprandial plasma CCK levels between the two groups. Outputs of exocrine pancreatic volume, protein and trypsin increased significantly after food in both control and nicotine treated groups of rats. The differences in outputs of volume and protein between the two groups of rats were not significant; however, the trypsin outputs in the nicotine rats were decreased significantly when compared to control rats. The data indicate that in rats, administration of food stimulated the release of immunoreactive gastrin and CCK with concomitant increase in exocrine pancreatic secretions of volume, protein and trypsin. Chronic nicotine treatment and its effect on food, however, appeared to have induced hyperfunction of G-cells that resulted in increased gastrin secretion and a decrease in trypsin secretion by exocrine pancreas. These data may have important implications in the etiology of the development of exocrine pancreatic dysfunction in chronic smokers.
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PMID:Meal-stimulated exocrine pancreatic secretion and release of GI peptides in normal and nicotine-treated rats. 204 42

The adaptation to a high protein diet of the concentration and mRNA level of a trypsin-sensitive, cholecystokinin-releasing peptide (monitor peptide), which was proposed to be the mediator of the cholecystokinin release in response to protein intake, was investigated in the rat pancreas. Adult rats were placed on one of two isocaloric diets. One group was fed a 22% casein diet (control diet) and the other a 64% casein diet (high-protein diet) for 14 days. In order to quantify the monitor peptide separately from pancreatic secretory trypsin inhibitor (PSTI-II), which is highly similar in its amino acid and mRNA nucleotide sequences to the monitor peptide but has less cholecystokinin-releasing activity, we used specific assay methods: HPLC was used for determining the monitor peptide concentration in zymogen granules and a synthetic oligonucleotide probe for determining the mRNA of the monitor peptide in the pancreas. The concentrations in the zymogen granules and the mRNA levels in the pancreas of the two peptides increased in parallel during the adaptation to the high protein diet, indicating that these two peptides were under the same control during the adaptation. The concentration and mRNA level of the monitor peptide, which were measured after 0, 3, and 14 days, increased throughout the experiment period, as did the concentration of trypsin. This suggested that the monitor peptide and trypsin may respond to similar signals during the adaptation to a high protein diet and that this apparent coordination may facilitate the adaptation of the pancreas to the diet.
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PMID:Effect of a high-protein diet on the gene expression of a trypsin-sensitive, cholecystokinin-releasing peptide (monitor peptide) in the pancreas. 206 78

The role of cholecystokinin (CCK) in the regulation of gastric emptying and pancreatic enzyme secretion was evaluated by infusing the CCK-receptor antagonist loxiglumide. Gastric emptying rates and pancreatic secretory outputs were measured in five healthy volunteers by the double-indicator perfusion technique using a multiple-lumen tube in the duodenum. Placebo or loxiglumide (22 mumol.kg-1.h-1) was infused throughout each experiment. Five hundred-milliliter liquid intragastric meals of (a) fat, protein, and glucose (Ensure; Abbott, Chicago, IL); (b) glucose, 20 g/dL; and (c) guar gum, 1.1 g/dL, were given in random order. In addition, the effect of a physiologic CCK-8 dose (20 pmol.kg-1.h-1) after an intragastric 500-mL saline meal (0.154 mol/L) was tested. Intravenous CCK-8 induced a marked retardation of the gastric emptying rate of the saline solution (P less than 0.05) while stimulating pancreatic secretory outputs; both effects were completely abolished by the infusion of loxiglumide. Loxiglumide markedly accelerated the gastric emptying rates (by approximately 40%) and simultaneously diminished lipase (by approximately 75%) and trypsin (by approximately 50%) outputs of both the mixed meal (P less than 0.01) and the pure glucose meal (P less than 0.05). Additional experiments using gamma camera scintigraphy confirmed the accelerating effect of loxiglumide on gastric emptying of the mixed meal (P less than 0.01). The gastric emptying rate of the guar meal, which did not release CCK, was not influenced by the infusion of loxiglumide. Loxiglumide distinctly augmented plasma CCK levels after the mixed (2.6 times) and the pure glucose (2.1 times) meals while markedly reducing (approximately 76%) pancreatic polypeptide release (P less than 0.02). It is concluded that endogeneous CCK exerts a major role in the regulation of both gastric liquid emptying and pancreatic secretion in humans.
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PMID:Role of cholecystokinin in the regulation of gastric emptying and pancreatic enzyme secretion in humans. Studies with the cholecystokinin-receptor antagonist loxiglumide. 206 26

It has been proposed that modulation of cholecystokinin (CCK) release by proteinases, proteinase inhibitors and protein is mediated by a pancreatic secretory trypsin inhibitor (PSTI), also called monitor peptide, in the rat. When human [125I]-PSTI was incubated with fasting small bowel juice or activated pancreatic juice greater than 88% of tracer eluted from gel chromatography in the characteristic position of hydrolysed PSTI. However, when the small bowel juice had been pre-incubated with soybean trypsin inhibitor 3 g/l, casein 5 g/l or lactalbumin 30 g/l, the hydrolysis of PSTI diminished so that 95%, 32%, and 33% respectively, now eluted in the characteristic position of free (i.e. intact and not bound to an enzyme) PSTI. When [125I]-PSTI was incubated with pure trypsin, chymotrypsin, elastase or enterokinase greater than 95% of tracer eluted in the position of PSTI-enzyme complex. Incubation of PSTI with trypsin plus one other enzyme was required to produce hydrolysis. The degree of protection of PSTI from hydrolysis in duodenal juice produced by these substances correlates with their affects on CCK release. Our findings support the hypothesis that PSTIs mediate the modulation of CCK release by intraluminal proteinases, proteinase inhibitors and proteins.
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PMID:Interactions of pancreatic secretory trypsin inhibitor in small intestinal juice: its hydrolysis and protection by intraluminal factors. 209 78

Cholecystokinin (CCK) was measured in an extract of porcine brain by a bioassay system based on the enzyme release from isolated pancreatic acini and a specific radioimmunoassay. The tissue extract represented a crude peptide preparation of porcine brain that contained several molecular forms of CCK, most of them of high molecular weight including CCK-58. The different molecular forms of CCK in the porcine brain extract were isolated by high performance liquid chromatography (HPLC). Determination of CCK-like bioactivity and immunoreactivity after HPLC was performed in parallel by bioassay and radioimmunoassay, respectively CCK-58 was the most abundant molecular form in the porcine brain extract, followed by CCK-33, and CCK-8. Both assay systems measured similar relative concentrations of all different molecular forms of CCK. To elucidate the biological potency of CCK-58 before and after tryptic cleavage, a CCK-58-enriched fraction was prepared by HPLC. Part of this material was quantitatively cleaved by trypsin resulting in the formation of small molecular forms of CCK. Bioactivity and immunoreactivity of equal amounts of cleaved and uncleaved material (= CCK-58) were determined by bioassay and radioimmunoassay in parallel. Cleavage of CCK-58 increased CCK-like bioactivity by 260% and CCK-like immunoreactivity by 310%. These results indicate that in a rat pancreatic acini system, porcine CCK-58 exerts 25-30% bioactivity compared to smaller CCK forms. The specific CCK antiserum G-160 seems to possess 25-30% affinity to CCK-58 in comparison to trypsin-cleaved CCK-58. It can be concluded that this antiserum exhibits an affinity to different molecular forms of CCK which parallels their relative bioactivity.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Measurement of tissue cholecystokinin (CCK) concentrations by bioassay and specific radioimmunoassay: characterization of the bioactivity of CCK-58 before and after tryptic cleavage. 212 97

The effect of pancreatic proteases or juice on the sodium oleate-stimulated pancreatic secretion and plasma concentrations of secretin and cholecystokinin in anesthetized rats was investigated. Each rat received sodium oleate in a dose of 0.12 mmol.h-1 via a duodenal tube. Sodium oleate infusion significantly increased pancreatic secretion (volume and protein output) compared with the saline given the control group. The increase in pancreatic secretion paralleled significant elevations of plasma concentrations of secretin and cholecystokinin. To determine a possible role of pancreatic proteases on the responses induced by sodium oleate, saline, chymotrypsin, and trypsin, a combination of chymotrypsin and trypsin or pancreatic juice was infused into the duodenum. The pancreatic secretion was significantly reduced by pancreatic proteases or pancreatic juice, and the reduction paralleled the decreases in plasma concentrations of the two hormones. These agents suppressed both pancreatic secretion and plasma hormone levels in the following order of magnitude: (pancreatic juice or chymotrypsin + trypsin) greater than (trypsin) greater than (chymotrypsin). The reduction of pancreatic secretion by pancreatic proteases was reversed by intravenous administration of secretin and cholecystokinin in physiological doses. It is concluded that negative-feedback regulation of pancreatic secretion is operative in the intestinal phase in rats and that both secretin and cholecystokinin are involved in the regulation.
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PMID:Effect of pancreatic proteases on plasma cholecystokinin, secretin, and pancreatic exocrine secretion in response to sodium oleate. 218 56

Urinary levels of immunoreactive insulin (IRI) were measured in 18 pigs subjected to pancreatic allograft transplantation with exocrine drainage into the urinary tract. Fifteen pigs were given no immuosuppressive therapy while 3 pigs received cyclosporine and prednisolone. The onset of rejection was defined as an increase in the serum levels of anionic trypsin (irAT). Urinary levels of IRI were compared between normo- and hyperglycemic pigs representing slow and fast rejectors. It was possible to measure insulin in the urine from all these pigs with a pancreatic allograft, and the urinary IRI levels increased after an intravenous injection of secretion and cholecystokinin. We found that urinary IRI response to secretin and cholecystokinin declined during rejection. By contrast, baseline, unstimulated urinary IRI levels did not correlate with rejection. No advantage was seen in the determination of urinary IRI when compared to determination of urinary irAT. In pigs not treated with immunosuppressants (with irreversible rejection), stimulated urinary levels of IRI and irAT were highly useful as graft-function indicators, whereas in immunosuppressed pigs (with reversible rejection episodes) they seemed to complement each other.
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PMID:Urinary insulin level as an indicator of graft function after porcine pancreatic transplantation. 219 41

This study analyzed the secretory pattern of pancreatic proteins released from the rabbit pancreas after acute stimulation of secretion by the cholecystokinin analog cerulein. To facilitate this, a new analytical approach utilizing high performance liquid chromatography (HPLC) was considered. Secretin (0.1 CU/kg x h) was intravenously infused in anaesthetized rabbits in combination with cerulein (0.05, 0.2 or 0.05 followed by 0.2 ug/kg x h) over 3 hours. Pancreatic juice was collected from the main pancreatic duct. The release of protein, amylase, trypsin and chymotrypsin was measured by conventional photometric methods, and the protein profiles were analyzed by reversed phase HPLC. Separation of pancreatic juice proteins by HPLC (Nucleosil 300-7 RP column; injection of 50 ul aliquots of samples normalized to 10 mg/ml protein concentration) resulted in a resolution of up to 16 peaks. Peaks representing amylase, prolipase, prophospholipase A2, procarboxypeptidases, chymotrypsinogen, trypsinogen, and glycoproteins were identified with some certainty by SDS-gel electrophoresis. Secretin infusion produced a small and short lasting rise in total protein secretion but lead to a persistent increase of fluid flow. The release of enzymes followed a mainly parallel pattern according to the photometric measurements. The resolution of the whole profile of pancreatic juice proteins by HPLC demonstrated only minor variations without a consistent or increasing tendency towards a preferential release of individual enzymes. Since even microheterogenities in the samples became apparent after HPLC, this approach would be sensitive enough to mirror effects like nonparallel release of enzymes.
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PMID:Protein profiles in rabbit pancreatic juice analyzed by HPLC after stimulation of secretion by secretin and cerulein. 227 58

A 61-residue cholecystokinin-releasing peptide (monitor peptide), which was obtained from rat pancreatic juice and found to stimulate pancreatic enzyme secretion, was recently reported to inhibit bovine trypsin and to possess epidermal growth factor (EGF)-like activities, at a concentration of about 10 nM. However, monitor peptide is structurally different from the EGF family of growth factors. To investigate whether monitor peptide contains the supposed EGF-like activities, it has been synthesized together with its [Ala23, Ala47] analog. The purified peptides, which were fully characterized by a range of methods including Cf-252 ionization mass spectrometry and enzymatic digestion to establish the locations of disulfide linkages, were shown to belong to the pancreatic secretory trypsin inhibitor family and not to the EGF family. Neither synthetic monitor peptide nor its analog were able to compete with 125I-EGF in A-431 cells or to stimulate growth of Swiss 3T3 and NRK 49F cells, up to 1 microM concentration. However, synthetic monitor peptide was as effective as the native product in the inhibition of trypsin. Replacement of the essential Arg23 in the [Ala23, Ala47]-analog led to loss of trypsin inhibition activity.
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PMID:Synthesis and properties of cholecystokinin-releasing peptide (monitor peptide), a 61-residue trypsin inhibitor. 227 71

Whereas pancreatic exocrine secretion in the rat varies considerably depending on the condition under which a study is performed, it is of great importance to study pancreatic pathophysiology in vivo, while the rat is conscious. In recent years several studies were performed in the conscious rat with a cannulated pancreatic duct, and much progress was made in delineating the role of cholecystokinin (CCK) in the regulation of pancreatic enzyme secretion in more detail. This progress was mainly due to the development of specific and sensitive radioimmunoassays for CCK and the availability of specific CCK-receptor antagonists. In the rat it was shown that a negative feedback regulation mechanism of pancreatic enzyme and CCK secretion exists in which intraluminal trypsin and, to a lesser extent, bile acids and plasma CCK, plasma secretin, and the cholinergic system play important roles. Probably by interference with this feedback mechanism in the rat, casein is a stronger stimulant of plasma CCK release and pancreatic exocrine secretion than fat. Finally, CCK does not play an important role in bombesin-stimulated pancreatic enzyme secretion in the rat.
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PMID:Role of cholecystokinin in the regulation of pancreatic enzyme secretion in the rat. 227 75


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