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)

In fasting rats, intraduodenal infusion of dilute hydrochloric acid results in significant increases in both pancreatic exocrine secretion and plasma concentration of secretin. To test the hypothesis that acid-induced release of secretin is mediated by a secretin-releasing factor (S-RF), anesthetized rats were prepared with pyloric ligation, duodenal and jejunal cannulas, and pancreatic duct cannulas. Donor rats were infused intraduodenally with 0.01 N HCl, 0.15 M NaCl, or a combination of 0.01 N HCl and 0.05 N NaHCO3 at 0.3 ml/min for 1.5 h, and the perfusates were collected via jejunal cannulas. The perfusates with pH adjusted to 6.0 were concentrated threefold and infused into the duodena of recipient rats. The concentrate of acid perfusate (CAP) significantly increased both pancreatic volume flow and bicarbonate output and plasma concentration of secretin, whereas concentrates of the saline perfusate (CSP) or the perfusate of a combination of 0.01 N HCl and 0.05 N NaHCO3 (CABP) did not influence pancreatic secretion or plasma concentration of secretin. The increased pancreatic secretion by CAP was attributed to increased circulating secretin because when secretin was immunoneutralized by a rabbit antisecretin serum, CAP-stimulated pancreatic secretion was abolished. The bioactivity of CAP was trypsin-sensitive and heat stable. The active substance in CAP had a molecular weight of less than 5,000 and greater than 1,000, as determined by ultrafiltration and bioassay. In conclusion, dilute HCl releases an S-RF into the upper small intestinal lumen to stimulate release of secretin. This substance, with molecular weight of less than 5,000, is heat stable and trypsin sensitive. Thus, the acid-stimulated release of secretin is mediated by a secretin-releasing peptide in the upper small intestinal lumen.
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PMID:Mechanism of acid-induced release of secretin in rats. Presence of a secretin-releasing peptide. 224 26

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

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

The development of exocrine pancreas function was studied in Swedish Landrace pigs surgically fitted with a chronic pancreatic duct catheter and a duodenal re-entrant cannula. The juice secretion and output of total protein and trypsin activity were followed before (basal secretion) and after feeding (postprandial secretion) during the first 1-13 weeks of life. The results showed that throughout the suckling period, up to 4-5 weeks of age, the basal pancreas function remained low and the secretory response to feeding, i.e., nursing sow milk, was also low. After weaning, the pancreatic juice secretion as well as the output of protein and trypsin activity markedly increased with respect to both basal and postprandial levels. Furthermore, the enzyme composition of the pancreatic juice changed qualitatively during this period. During the first 2 weeks of life, the intravenous administration of cholecystokinin (CCK) and secretin did not stimulate exocrine function, but a significant effect was achieved from 3-4 weeks of age. These results showed that there was both an increase in exocrine pancreas function and a qualitative change in the hydrolytic enzyme pattern during porcine postnatal ontogeny, apparently correlated with the changes in diet around weaning. An increase in the response of the pancreas to hormonal stimulation was also observed during the suckling period.
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PMID:Development of exocrine pancreas function in chronically cannulated pigs during 1-13 weeks of postnatal life. 230 71

The effect of intraduodenally administered cattle bile (CB) and Na-taurodeoxycholate (TDC) on basal pancreatic secretion and plasma levels of secretin, pancreatic polypeptide (PP), and gastrin were investigated on two separate days in 10 fasting volunteers. Doses of 2-6 g CB and 200-600 mg TDC were given intraduodenally at 65-min intervals. Volume, bicarbonate, lipase, trypsin, amylase, and bilirubin were measured in 10-min fractions of duodenal juice, and GI peptides determined by radioimmunoassay. CB and TDC enhanced significantly and dose-dependently volume, bicarbonate and enzyme secretion, and plasma secretin and PP levels. In contrast, plasma gastrin showed only a marginal increase. We conclude that the hydrokinetic effect of intraduodenal CB and TDC is at least partially mediated by secretin. Gastrin could be ruled out as a mediator of the ecbolic effect, whereas other GI peptides, primarily CCK, and/or neural mechanisms must be considered possible mediators. Both pathways may also play a role in the PP release observed.
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PMID:Effect of intraduodenal bile and Na- taurodeoxycholate on exocrine pancreatic secretion and on plasma levels of secretin, pancreatic polypeptide, and gastrin in man. 230 5

During the storage of secretin in acid and neutral aqueous solutions, five degradation peptides (A1, A2, A3, A4, A5) and one degradation peptide (N1) were produced, respectively. They were isolated in pure form by HPLC, and the intramolecular structures were studied by a combination of amino acid analysis, enzymatic digestions, HPLC, and Fab-mass spectroscopy. Although the degradation peptides are composed of the same amino acids as secretin after acid hydrolysis (except A1 and A4 which are cleavage products S16-27 and S4-27, respectively), reversed-phase HPLC analysis of their digestive fragments with trypsin and alpha-chymotrypsin are different from those of secretin. By Fab-mass spectroscopy, the m/z values for the S1-6 fragments obtained from secretin, A2, and A3 were 663, 663, and 645, respectively. When S1-6 from A2 was treated with aminopeptidase M, a fragment obtained was identical with the synthetic beta-aspartyl3 S3-6, as determined by HPLC. The A2 and N1 peptides are completely the same based on various chemical analyses. The A3 peptide can also be rapidly degraded to secretin and beta-aspartyl3 secretin. Consequently, A1 and A4 are concluded to be the cleavage peptides of secretin, S16-27 and S4-27, respectively, A2 and N1 are concluded to be beta-aspartyl3 secretin, and A3 is concluded to be aspartoyl3 secretin.
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PMID:Degradation peptides of secretin after storage in acid and neutral aqueous solutions. 231 77

We examined the effect of fasting on the course of experimental acute pancreatitis induced in rats by four subcutaneous injections of 20 micrograms/kg body weight of cerulein at hourly intervals. Rats were either fasted from 24 hr before to 9 hr after the first cerulein injection or fed ad libitum throughout the experiment. Twenty-four hours of fasting reduced cerulein-induced increases in serum levels of amylase and anionic trypsin(ogen) to 50 and 70% of those in fed rats, respectively. Increases in pancreatic wet weight after cerulein injections were also less in fasted rats than in fed rats. Pancreatic content of trypsin was significantly decreased after a 24-hr fast, and no further changes were induced by cerulein injections. The histological signs of acute pancreatitis were greatly alleviated by fasting. However, 24 hr of fasting did not alter the sensitivity and responsiveness of the exocrine pancreas to cerulein in both in vivo and in vitro. Plasma CCK bioactivity and immunoreactive secretin concentration in 24-hr-fasted rats were significantly lower than those in fed rats. Administration of CCK receptor antagonist, loxiglumide, 12 hr prior to the induction of acute pancreatitis reduced the increase in serum amylase activity in fed rats to nearly the same levels as that in fasted rats and alleviated histological signs of pancreatitis to some extent. These present observations suggest that fasting lessens the severity of cerulein-induced acute pancreatitis by reducing endogenous CCK release.
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PMID:Fasting prevents acute pancreatitis induced by cerulein in rats. 236 38

By means of consecutive pancreatic stimulation, we have investigated the presence of changes of pancreatic function in alcoholic patients, with and without alcoholic liver disease, in order to detect functional alterations and possible association of hepatic and pancreatic disease. The patients were 49 chronic alcoholics (8 patients without liver disease, 11 hepatic steatosis, 9 alcoholic hepatitis and 21 alcoholic cirrhosis) and 15 non alcoholic subjects (8 normal controls and 7 cases of non alcoholic cirrhosis). In all the cases two consecutive stimulations were carried out: first with secretin and cholecystokinin (CCK) and second with CCK alone. The total volume and concentration as well as the output of bicarbonate, trypsin, amylase and total proteins were measured in the duodenal juice. Patients with alcoholic cirrhosis had larger volumes of duodenal juice and lower concentrations of bicarbonate, enzymes and proteins. There was also a tendency to larger volume and lower bicarbonate concentration as the hepatic lesion was more severe. Bicarbonate output was significatively higher in patients with alcoholic cirrhosis but for the remaining parameters the outputs were similar in all the groups. In conclusion, the alterations in pancreatic function parallel the severity of the liver disease. None of the patients had changes consistent with chronic pancreatitis.
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PMID:[Changes in pancreatic secretion in alcoholic liver disease]. 237 59

A standard duodenal perfusion/aspiration technique was used to continuously monitor biliary and pancreatic excretion in young healthy human subjects, and the excretory patterns were examined by Fourier power spectral analysis. Experiments were carried out in the fasting state, either without or during a continuous parenteral (i.v.) stimulation by secretin and the cholecystokinin analogue ceruletide. The duodenal content aspirated was either discarded after sampling or reinfused into the jejunum. In the fasting state, significant biliary and pancreatic excretion was detected, fluctuating with a periodicity of about 60 min. During parenteral infusion with ceruletide/secretin, to simulate a postprandial state, the rate of biliary and pancreatic excretion increased as compared with fasting levels alone (basal levels). A dominant period of about 60 min was still detected but second periods of approximately 45 min and approximately 95 min, respectively, were also observed. The peak power and the total power of the biliary excretion signals were reduced. Reinfusion of aspirated duodenal fluid into the intestine (jejunum) led to a further decrease in peak power and total power of the known biliary signals. Trypsin excretion into the duodenum revealed mainly insignificant changes in peak and total power upon hormone stimulation despite a definite increase in total amount of trypsin excreted. The results indicate that parenteral ceruletide/secretin stimulation has a stabilizing effect on biliary excretion in man, and that reinfusion of aspirated duodenal content into the intestine further stabilizes the excretion.
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PMID:Fourier analysis of biliary and pancreatic excretion in man based on data obtained by a duodenal perfusion/aspiration technique. 239 97

The effect of ranitidine (20 mg . kg-1) and cimetidine (50 mg . kg-1) on pancreatic secretory and trophic responses to caerulein (1 microgram . kg-1) was studied in the rat. Ranitidine or cimetidine were administered alone or combined with caerulein twice a day for 7 days. Saline-treated rats were used as controls. At the end of treatment animals were anesthetized and pancreatic juice was collected for 1 h after intravenous secretin plus CCK-PZ (8 U . kg-1). Afterwards rats were sacrificed and growth and composition of pancreatic tissue were determined. Compared with control (saline) values, volume of pancreatic juice and output of trypsin and amylase were increased by treatment with caerulein. Ranitidine, when given combined with caerulein, completely abolished the secretory response induced by the peptide, whereas it was totally ineffective when given alone. Cimetidine (alone or combined with caerulein) was always ineffective. Caerulein increased pancreatic weight, total pancreatic trypsin, amylase and RNA content. Here again ranitidine, combined with caerulein, abolished almost completely the trophic effect of caerulein on the pancreas, but when given alone it did not influence pancreatic growth and composition. Also in this case, cimetidine was completely inactive. These results suggest that ranitidine affects exocrine pancreas with an action independent of the H2-receptor blockade.
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PMID:Inhibition of pancreatic secretory and trophic response to caerulein by the H2-receptor antagonist ranitidine in the rat. 240 51


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