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)

The mechanism by which physiological concentrations of cholecystokinin (CCK) evoke pancreatic exocrine secretion in humans was investigated. CCK octapeptide (CCK-8) dose dependently increased trypsin and lipase output in healthy humans. Atropine inhibited CCK-8 (10 ng.kg-1.h-1)-stimulated trypsin output by 84.0 +/- 7.7% and lipase output by 78.6 +/- 9.2%. The inhibition with atropine was much less with a CCK-8 dose of 40 ng.kg-1.h-1 (41.8 +/- 6.6% for trypsin and 46.3 +/- 7.3% for lipase). CCK-8 at 10 ng.kg-1.h-1 produced plasma CCK levels similar to postprandial levels (6.0 +/- 1.3 vs. 6.9 +/- 0.8 pM), whereas the 40-ng.kg-1.h-1 dose produced supraphysiological levels (18.4 +/- 3.1 pM). To evaluate if CCK might act via stimulation of cholinergic nerves, in vitro studies were performed using rat pancreas. CCK-8 (10 nM-10 microM) stimulated [3H]acetylcholine release from pancreatic lobules that was blocked by tetrodotoxin, a calcium-free medium, and the CCK antagonist L364,718. In conclusion, CCK-stimulated pancreatic enzyme secretion is dependent on cholinergic neural and noncholinergic pathways. In humans, CCK infusions, which produce plasma CCK levels similar to those seen postprandially, stimulate the pancreas predominantly via a pathway dependent on cholinergic innervation. Correlative in vitro experiments suggest that CCK may act by stimulation of neural acetylcholine release. In contrast, supraphysiological CCK infusions act in part via noncholinergic pathways.
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PMID:Cholecystokinin at physiological levels evokes pancreatic enzyme secretion via a cholinergic pathway. 163 5

We examined the effect of bombesin on plasma trypsin release and exocrine pancreatic secretion in dogs. Bombesin significantly increased plasma immunoreactive trypsin (IRT). Atropine significantly inhibited the response of plasma IRT to bombesin. Pancreatic trypsin secretion was also increased by bombesin, as well as bicarbonate and protein outputs. Atropine failed to inhibit pancreatic trypsin secretion. In conclusion, bombesin has a stimulatory effect on plasma trypsin release mediated by a cholinergic mechanism and different from pancreatic secretion.
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PMID:Stimulatory effects of bombesin on plasma trypsin release and exocrine pancreatic secretion in dogs. 170 3

In acute experiments on dogs it has been established that intraduodenal administration of trypsin, amylase and lipase induces selective inhibition of the introduced enzyme secretion by the pancreas. Atropine injection (0.2 mg/kg, intravenously, 4 times/h) removes the inhibitory effect of the introduced enzymes, the most pronounced atropine action being recorded in respect to trypsin. Intraduodenal trypsin administration decreases non-selective inhibitory effect of atropine on the stimulated secretion of the pancreas. It has been concluded that not only duodenal regulatory peptides but also the M-cholinergic mechanism participate in the selective inhibition.
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PMID:[Mechanisms of selective inhibition of pancreatic secretion after increasing the enzymatic activity of duodenal contents]. 171 28

The effect of atropine on the feedback regulatory mechanism of pancreatic enzyme secretion exerted by intraluminal trypsin was investigated in conscious rats. Intravenous atropine infusion (50 micrograms/kg/h) suppressed pancreatic enzyme secretion to the same extent in both the presence and the absence of pancreatic juice in the intestine. However, with or without atropine infusion, pancreatic secretory rate was higher throughout diversion of pancreatic juice than during intraduodenal return of the juice. Atropine also inhibited the stimulatory response to intraduodenal trypsin inhibitor and intravenous caerulein. The atropine-induced inhibitory effect was not significantly different between the two experimental conditions. Regardless of atropine administration, both trypsin inhibitor and caerulein caused a significant increase in pancreatic secretion. The results suggest that cholinergic mechanisms have little influence on the feedback regulation. Cholinergic mechanisms may play an important role in maintaining the physiologically basal secretion because the basal secretion is atropine-sensitive.
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PMID:Effect of atropine on feedback regulation of pancreatic enzyme secretion in rats. 245 64

This study was undertaken to determine the effect of atropine and somatostatin, two inhibitors of intraduodenal pancreatic enzyme secretion, on bombesin-stimulated release of plasma immunoreactive trypsin in 6 healthy volunteers. Infusion of 5 ng/kg.min bombesin during 30 min induced significant increases in plasma trypsin from 206 +/- 20 to 334 +/- 44 ng/ml (p less than 0.01). Atropine (15 ng/kg as i.v. bolus followed by 5 ng/kg.h) had no influence on the bombesin-stimulated increase in plasma immunoreactive trypsin (207 +/- 20 to 326 +/- 54 ng/ml). Somatostatin (125 micrograms as i.v. bolus followed by 125 micrograms/h) also failed to inhibit the plasma trypsin response to bombesin (207 +/- 18 to 663 +/- 166 ng/ml). These results point to major differences in the regulation of plasma and intraduodenal trypsin secretion.
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PMID:Effect of atropine and somatostatin on bombesin-stimulated plasma immunoreactive trypsin release in man. 288 97

Potentiating action between secretin and cholecystokinin on exocrine pancreatic secretion of bicarbonate has been well recognized. In the present study, we studied the effect of atropine on potentiating action on pancreatic exocrine secretion stimulated by exogenous secretin in physiologic dose and cholecystokinin-octapeptide in humans. Using a dye-dilution technique and a duodenal triple-lumen tube, pancreatic secretion of both bicarbonate and trypsin was determined while gastric juice was completely aspirated. Secretin given i.v. in a dose of 2.7 pmol/kg/h, which was known to achieve a similar plasma concentration of secretin after meal in humans, and cholecystokinin-octapeptide 26.2 pmol/kg/h potentiated pancreatic secretion of bicarbonate but not the pancreatic trypsin output. Atropine given i.v. in a dose of 1 mg/h abolished the potentiation effect of the two hormones on pancreatic bicarbonate output. Since the inhibitory effect of atropine on the secretin-stimulated bicarbonate output was statistically significant, the major inhibitory effect of atropine on the potentiation of pancreatic bicarbonate secretion appears to be its effect on the action of secretin.
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PMID:Atropine abolishes the potentiation effect of secretin and cholecystokinin-octapeptide on exocrine pancreatic secretion in humans. 336 47

In seven healthy volunteers insulin-induced hypoglycemia caused a significant rise in free serum cationic trypsin-like immunoreactivity (CTLI), which could be blocked by atropine. Atropine alone significantly decreased the serum CTLI level. The inhibitory effect of atropine was augmented by insulin, which appears to be a peripheral inhibitor of the CTLI release from the pancreatic acinar cells.
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PMID:The effect of insulin-induced hypoglycemia and atropine on serum cationic trypsin-like immunoreactivity in man. 639 9

The cephalic phase of pancreatic secretion in humans was investigated using modified sham feeding and a duodenal perfusion system. Studies performed in 5 normal volunteers were designed so that trypsin and bicarbonate outputs during sham feeding, with or without pretreatment with atropine, were compared to "maximal" pancreatic secretory response to exogenous stimulation with caerulein and secretin. The role of gastric acid entry to the duodenum in mediating cephalic responses was assessed by a comparison between outputs observed when gastric aspiration (congruent to 80% efficient) was used alone and when acid entry was completely abolished by combining gastric aspiration with cimetidine pretreatment. To evaluate the role, if any, of gut hormone release in the pancreatic secretory response to sham feeding, plasma gastrin and cholecystokinin concentrations were monitored throughout. Trypsin outputs during sham feeding were 31.9 +/- 10.45 kallikrein inactivator units per 30 min, equivalent to four times basal output and 92% of maximal, but were only 54% maximal in subjects pretreated with cimetidine. Atropine suppressed basal trypsin output and abolished the response to sham feeding (4.98 +/- 3.89 kallikrein inactivator units per 30 min). A modest increase in bicarbonate secretion during sham feeding (3.30 +/- 1.97 mmol/30 min versus basal of 0.68 +/- 0.74 mmol/30 min, p = 0.5) was not influenced by atropine but was abolished by cimetidine pretreatment. No significant changes in plasma gastrins were observed in these studies and plasma cholecystokinins remained undetectable throughout. We conclude that there is tonic vagal stimulation of trypsin secretion, and that sham feeding markedly increases trypsin output, which is augmented further by acid entry into the duodenum. There is no direct effect of cephalic stimulation on bicarbonate secretion or on gastrin or cholecystokinin release.
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PMID:Sham feeding and pancreatic secretion. Evidence for direct vagal stimulation of enzyme output. 672 52

We have investigated whether hormonally mediated negative feedback mechanisms regulate pancreatic exocrine secretion in guinea pigs. In anesthetized guinea pigs prepared with a tube in the proximal duodenum, pyloric ligation, and pancreatic duct cannulation with PE-10 tubing, diversion of pancreatic juice for as long as 4 h in fasting states failed to increase either pancreatic secretion or plasma levels of secretin or cholecystokinin (CCK). In the same animal preparation, intraduodenal (ID) infusion of sodium oleate (SO) resulted in significant increases in both pancreatic secretin and plasma levels of the two hormones that were significantly suppressed by ID infusion of pancreatic juice or a combination of trypsin and chymotrypsin. In another group of guinea pigs, this significant increase in pancreatic secretion was profoundly suppressed by a rabbit antisecretin serum (0.2 ml) or loxiglumide (10 mg.kg-1.h-1). Moreover, a combination of the antiserum and loxiglumide completely abolished the pancreatic secretion. The effect of atropine, 20 micrograms.kg-1.h-1 i.v., on SO-stimulated pancreatic secretion and hormone release was also studied. Atropine completely suppressed the pancreatic secretion of volume flow, bicarbonate, and protein stimulated by SO, whereas neither one of the two hormone levels was affected by intravenous atropine, indicating that atropine blocks the actions of both secretin and CCK on the pancreatic exocrine secretion. It is concluded that a negative feedback regulation of exocrine pancreatic secretion is operative in the intestinal phase of pancreatic secretion in guinea pigs and that this feedback mechanism is mediated by both secretin and CCK. Furthermore, in guinea pigs, cholinergic tone plays an important modulating role in the mechanism.
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PMID:Negative feedback regulation of pancreatic exocrine secretion in guinea pigs. 771 42

Small fluctuations in cholinergic input may be involved in the regulation of human interdigestive pancreatic secretion. To determine the effects of small changes in cholinergic tone on phase II interdigestive trypsin secretion, we gave cholinergic agonists or antagonists to 17 healthy fasting subjects who underwent gastrointestinal intubation. Duodenal trypsin outputs, gastroduodenal motility, and plasma levels of pancreatic polypeptide (PP) as a marker of cholinergic tone were measured during intravenous infusion of bethanechol (0, 5, or 40 micrograms.kg-1.h-1) or atropine (0, 4, or 16 micrograms.kg-1.h-1) given during phase II alone or in combination based on a 3 x 3 factorial design. Data were evaluated by a response surface analysis of the average log values for the test period (using the average of log values of the control period as a covariate). Bethanechol increased trypsin output (p < 0.05) and plasma concentrations of PP (p < 0.05) within the ranges of spontaneous fluctuations of trypsin output and PP during phase II, but did not disrupt the periodicity of pancreatic secretion or the characteristic cyclical pattern of interdigestive motility and induction of phase III activity. Atropine markedly decreased trypsin output (p < 0.05) and plasma concentrations of PP (p < 0.05) and abolished the cycling of interdigestive pancreatic secretion and motor activity. These data suggest the hypothesis that cholinergic pathways participate in the control of interdigestive pancreatic secretion during phase II, while enzyme secretion during phase III may be regulated by other mechanisms.
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PMID:Cholinergic regulation of phase II interdigestive pancreatic secretion in humans. 809 37


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