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:3.4.21.4 (trypsin)
42,187 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

Influences of fat on release of insulin, growth hormone and pancreatic enzyme secretion were studied in 35 metabolically healthy subjects. A fat solution containing 40 g of soy bean oil was administered, I.V., orally and intraduodenally. In all cases there was a similar increase of insulin but the rise in serum insulin after oral or intraduodenal fat administration was not related to the changes in plasma free fatty acids, free glycerol and triglyceride levels. Blood surgar responded according to insulin secretion. The route of fat administration may possibly influence growth hormone secretion. Following intraduodenal fat administration volume and bicarbonate contents of the duodenal juice rose slightly whereas trypsin and bilirubin content increased considerably. These results suggest that insulin secretion after oral or intraduodenal administration of fat is influenced by intestinal factors. Cholecystokinin-pancroezymin and gastric inhibitory polypeptide are qualified to serve as such factors.
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PMID:Effect of lipids on insulin, growth hormone and exocrine pancreatic secretion in man. 120 69

Exocrine pancreatic function was studied after meal stimulation and intravenous hormone stimulation with secretin and cholecystokinin in 10 patients with duodenal ulcers before, and 3 to 4 months after, highly selective vagotomy. Hormone stimulation was also performed in 10 healthy volunteers. Meal stimulation test results pre- and postoperatively were not certainly different, but it was concluded that the test technique was inappropriate to the study, not least because no correction of aspirated volumes is possible. Such correction was possible in the intravenous hormone studies. A gastroduodenal tube with a balloon to occlude the pyloric canal was used, and tracer was infused into the duodenum. Results of this latter study showed that patients with duodenal ulcer display an increased basal secretion volume and an increased trypsin output during hormone stimulation. After highly selective vagotomy, basal secretion volume fell, tending to normal, while the stimulated secretion volume and bicarbonate and enzyme output were unchanged.
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PMID:The effects of highly selective vagotomy on exocrine pancreatic function in man. 125 38

Ten subjects received secretin and cholecystokinin or, in duplicate tests, the two hormones together with either diazepam or diazepam plus hyoscine butylbromide in order to determine whether these drugs, which are often used during retrograde endoscopic cannulation of the pancreatic duct, affect pancreatic and biliary secretion in response to the hormones. Diazepam with hyoscine butylbromide reduced the secretion of trypsin into the duodenum and delayed the appearance of both trypsin and bilirubin in duodenal aspirate. These effects must be taken into account when interpreting pancreatic and biliary responses measured during direct cannulation of the pancreatic duct.
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PMID:Effect of diazepam and hyoscine butylbromide on response to secretin and cholecystokinin-pancreozymin in man. 127 18

Pancreatic nodules were produced in rats by either feeding raw soya flour alone or by injection of azaserine plus raw soya flour feeding. The resulting nodules were studied to determine whether there was any functional difference between this tissue and the relatively normal internodular pancreas. Tissue DNA and trypsin content were significantly elevated in nodules compared to the adjacent tissue. With fasting, protein and enzyme content increased significantly and equally in both nodular and internodular tissues. RNA levels fell significantly and the decrease was more pronounced in nodular tissue. The responsiveness of the multinodular pancreas to cholecystokinin was examined by measuring pancreatic secretion basally and in response to cholecystokinin. Both the volume and protein content secreted by the multinodular pancreas were greatly elevated above control levels. When corrected for pancreatic weight, the difference remained significant and appeared to be due to increased basal secretion by the nodular pancreas. These studies demonstrate that azaserine-raw soya flour induced nodules are functionally efficient. Furthermore, the secretory response to cholecystokinin of these nodules is equal to or higher than that of normal tissue.
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PMID:The effect of fasting and cholecystokinin stimulation on normal and neoplastic tissue in the rat pancreas. 127 37

Peptide YY (PYY) and neuropeptide Y (NPY) inhibit agonist-induced adenosine 3',5'-cyclic monophosphate (cAMP) production and pepsinogen secretion from chief cells. We used radiolabeled PYY and NPY to characterize receptors on chief cells from guinea pig stomach. Binding of 125I-labeled PYY was rapid (70% maximal within 10 min) and specific (not inhibited by secretin, vasoactive intestinal peptide, cholecystokinin, carbachol, prostaglandin E2, forskolin, or cholera toxin). Measurement of the ability of PYY to inhibit binding of 125I-PYY indicated the presence of 1.8 x 10(3) high-affinity [dissociation constant (Kd) = 1.7 nM] and 5.1 x 10(4) low-affinity (Kd = 83.3 nM) sites/cell. Internalization of bound 125I-PYY was suggested by slow and incomplete dissociation in the presence of unlabeled PYY (50% after 2 h) and was examined further by measuring residual binding after washing with acetic acid (pH 2.5), glycine (pH 10.5), or trypsin. After 30 min at 37 degrees C, internalization of radioligand was evidenced by the failure of washing with these solutions to remove 50-65% of bound radioactivity. At 4 degrees C, internalization of 125I-PYY was nearly abolished. Binding of 125I-PYY and 125I-NPY was inhibited by NPY-(13-36) but not by [Leu31,Pro34]NPY indicating that these are Y2 receptors. In guinea pig chief cells, PYY and NPY modulate cAMP-mediated pepsinogen secretion by interacting with specific high-affinity Y2 receptors.
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PMID:Y2 receptors for peptide YY and neuropeptide Y on dispersed chief cells from guinea pig stomach. 131 99

1. The effects of a diet rich in protein and fat, compared with a control diet, with or without chronic ingestion of ethanol on the pancreatic response to cholecystokinin were studied in rats after a 7-month treatment period. The acute effects of intraduodenal administration of 20% (v/v) ethanol were also analysed under these experimental conditions. 2. Animals receiving a diet rich in protein and fat showed a greater percentage increase in pancreatic output in response to cholecystokinin. 3. Chronic ethanol consumption reduced the basal secretion of protein and amylase; and even though the response capacity to cholecystokinin (considered as the percentage secretion on cholecystokinin stimulation with respect to basal secretion) was maintained, this led to hormone-stimulated secretion being decreased in comparison with the animals receiving water. In contrast, a lack of inhibition of basal volume flow and flow after cholecystokinin stimulation was seen after long-term ingestion of ethanol. 4. Acute administration of ethanol generally depressed cholecystokinin-stimulated pancreatic secretion. 5. On stimulation with cholecystokinin, the diet rich in protein and fat combined with long-term ingestion of ethanol led to non-parallel changes in the release of pancreatic enzymes, since an increase in trypsin secretion and a decrease in amylase secretion occurred concomitantly.
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PMID:Effect of acute and chronic administration of ethanol on the pancreatic exocrine response to cholecystokinin in rats fed different diets. 131 54

Intrahepatic bile duct epithelial cells, or cholangiocytes, contribute to bile secretion in response to hormones, including secretin. However, the mechanism by which secretin stimulates ductular bile flow is unknown. Since recent data in nonhepatic epithelia have suggested a role for exocytosis in fluid secretion, we tested the hypothesis that secretin stimulates exocytosis by isolated cholangiocytes. Cholangiocytes were isolated from normal rat liver by a newly described method employing enzymatic digestion and mechanical disruption followed by immunomagnetic separation using specific monoclonal antibodies, and exocytosis was measured using a fluorescence unquenching assay employing acridine orange. Secretin caused a dose-dependent (10(-12)-10(-7) M) increase in acridine orange fluorescence by acridine orange-loaded cholangiocytes with a peak response at 10 min; the half-maximal concentration of secretin was 7 x 10(-9) M. The secretin effect was inhibited by preincubation of cholangiocytes with colchicine (30% inhibition, p less than 0.05) or trypsin (90% inhibition, p less than 0.001); no inhibition was seen with lumicolchicine and heat-inactivated trypsin. Cholecystokinin, insulin, and somatostatin had no effect on fluorescence of acridine orange-loaded cholangiocytes; secretin had no effect on fluorescence of acridine orange-loaded hepatocytes or hepatic endothelial cells. Exposure of isolated cholangiocytes to secretin at doses that stimulated exocytosis caused a dose-dependent increase in cyclic AMP levels (218% maximal increase, p less than 0.05); moreover, an analogue of cyclic AMP stimulated exocytosis by cholangiocytes. Secretin had no effect on intracellular calcium concentration using Fura-2-loaded cholangiocytes assessed by digitized video microscopy. Our results demonstrate, for the first time, that secretin stimulates exocytosis by rat cholangiocytes. The effect is cell- and hormone-specific, dependent on intact microtubules, on a protein(s) on the external surface of cholangiocytes, and on changes in cellular levels of cyclic AMP. The results are consistent with the hypothesis that secretin-induced changes in bile flow may involve an exocytic process.
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PMID:Secretin stimulates exocytosis in isolated bile duct epithelial cells by a cyclic AMP-mediated mechanism. 132

The regulation of acid secretion was clarified by the development of H2-receptor antagonists in the 1970s. It appears that gastrin and acetylcholine exert their effects on acid secretion mainly by stimulation of histamine release from the enterochromaffin-like (ECL) cell of the fundic gastric mucosa. The isolated ECL cell of rat gastric mucosa responds to gastrin/cholecystokinin (CCK), acetylcholine, and epinephrine with histamine release and to somatostatin and R-alpha-methyl histamine by inhibition of histamine release. Histamine and acetylcholine stimulate the parietal cell by elevation of cAMP or [Ca]i by activation of H2 or M3 receptors, respectively. These independent pathways converge to activate the gastric acid pump, the H+,K+ ATPase. Activation is a function of the association of the ATPase with a potassium chloride transport pathway that occurs in the membrane of the secretory canaliculus of the parietal cell. Hence the secretory canaliculus is the site of acid secretion, the acid being pumped into the lumen of the canaliculus. The pump is composed of two subunits, a large catalytic and a smaller glycosylated protein. This final step of acid secretion has become the target of drugs also designed to inhibit acid secretion. The target domain of the benzimidazole class of acid pump inhibitors is the extracytoplasmic domain of the pump that is secreting acid, and the target amino acids are the cysteines present in this domain. The secondary structure of the pump can be analyzed by determining trypsin-sensitive bonds in intact, cytoplasmic-side-out vesicles of the ATPase, and it has been shown that the alpha subunit has at least eight membrane-spanning segments. Omeprazole, the first acid pump inhibitor, forms a disulfide bond with cysteines in the extracytoplasmic loop between the fifth and sixth membrane-spanning segment and to a cysteine in the extracytoplasmic loop between the seventh and eight segments, preventing phosphorylation of the pump by ATP. As a result of the effective and long-lasting inhibition of acid secretion by the acid pump inhibitor, superior clinical results have been found in all forms of acid-related disease.
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PMID:Acid secretion and the H,K ATPase of stomach. 134 Oct 65

Somatostatin 28 (S-28), originating in gastrointestinal cells, is secreted into the circulation and increases in humans after ingestion of a mixed meal. To evaluate the possibility that the increased levels of S-28 post cibum might modulate the release of enzymes and bicarbonate from the exocrine pancreas, S-28 was infused intravenously into healthy volunteers to levels seen after food intake. During S-28 infusion, the output of lipase, trypsin, amylase, and bicarbonate stimulated by either exogenous cholecystokinin octapeptide or endogenous signals from intraduodenal administration of tryptophan or a mixture of amino acids was significantly reduced. It is concluded that S-28 released from the gut during food intake modulates pancreatic exocrine function in humans.
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PMID:Evidence for hormonal inhibition of exocrine pancreatic function by somatostatin 28 in humans. 135 58


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