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)

Both immunoreactive intact cholecystokinin (CCK33) and its COOH-terminal octapeptide (CCK8) are detected in brain and gut extracts of monkey, dog, and pig using an antiserum with equivalent sensitivities for detecting CCK8 in the free form or when incorporated in the intact molecule. The failure to detect intact cholecystokinin in extracts from monkey or dog by using an antiserum developed by immunization with porcine CCK33 is due to marked species differences in the NH2-terminal portion of the molecule. Immunohistochemical staining reveals the presence of CCK peptides in rabbit cerebral cortical tissue neurons. Subcellular fractionation of rat cerebral cortical tissue demonstrates that CCK immunoreactivity is concentrated in the pellet identified by electron microscopy to contain a high proportion of synaptic vesicles. A converting enzyme that differs from trypsin has been partially purified from canine and porcine cerebral cortical extracts. It converts porcine CCK to smaller immunoreactive forms, but fails to convert big gastrin to heptadecapeptide gastrin. This enzyme differs from trypsin not only in substrate specificity but also in several physicochemical properties. Cerebral cortical extracts from hyperphagic ob/ob mice have strikingly lower contents of CCK than those from their lean littermates and other normal mice. These studies taken together are consistent with a role for CCK as a neurotransmitter involved in the overall regulation of appetite.
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PMID:Gastrointestinal peptides in the brain. 11 Jun 22

Isolated gastric smooth muscle cells were prepared from the stomach of Bufo marinus by successive incubation in collagenase without added trypsin. Contraction was determined by image-splitting micrometry and expressed as the mean percentage decrease in cell length from control. Peak contractile response was attained within 30 s. Dose-response curves constructed from peak responses showed that the maximal responses to CCK-OP (37.2 +/- 3.8%), acetylcholine (35.3 +/- 2.5%), and Ca2+ (42.3 +/- 0.9%) were similar. The D50s for octapeptide of cholecystokinin (CCK-OP) and acetylcholine were around 10(-12) M and 10(-11) M, respectively. The response to a combination of submaximal concentrations of acetylcholine and CCK-OP exceeded the individual responses but did not exceed the maximal response to either agent alone. A low concentration of atropine (5 X 10(-10) M) inhibited specifically the maximal response to acetylcholine. A high concentration of atropine (5 X 10(-8) M) inhibited partially the maximal response to CCK-OP but had no effect on the maximal response to Ca2+. It was concluded that 1) dispersed gastric smooth muscle cells are highly sensitive to stimulation; 2) CCK-OP has a direct (myogenic) contractile effect on gastric smooth muscle; and 3) the effect of CCK-OP and acetylcholine are mediated by separate receptors.
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PMID:Interaction of acetylcholine and cholecystokinin with dispersed smooth muscle cells. 11 64

An enzyme has been partially purified from canine and porcine cerebral cortical extracts that differs from trypsin in that it manifests some degree of hormone specificity since it converts porcine cholecystokinin to smaller immunoreactive forms, i.e., the COOH-terminal dodecapeptide and octapeptide fragments, but fails to convert big gastrin (34 amino acids) to heptadecapeptide gastrin. This enzyme is distinguishable from trypsin not only in substrate specificity, but also in several physiochemical properties. It is not inhibited in the presence of concentrations of lima bean trypsin inhibitor sufficient to inhibit 1 mg of trypsin per ml of incubation mixture. It is inactivated when incubated with substrate at 45 degrees C for 1 hr, whereas trypsin remains fully active when incubated under the same conditions at 55 degrees C. The enzyme elutes in the void volume on Sephadex G-50 and G-75 gel filtration. On sucrose gradient centrifugation, the proteolytic activity associated with trypsin is recovered above albumin but that of the solubilized brain enzyme is recovered below gamma globulin. The enzyme is not detectable in splenic extracts, which do contain nonspecific proteases capable of completely degrading cholecystokinin. Further investigation is required to determine whether the enzyme in the gut that converts cholecystokinin to the bioactive and immunoactive COOH-terminal fragments resembles or is different from the brain converting enzyme.
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PMID:Characterization of a nontrypsin cholecystokinin converting enzyme in mammalian brain. 28 18

Residual beta cell function was studied in 18 juvenile-onset diabetics by measuring serum C-peptide immunoreactivity (CPR) fasting, and after IV injection of glucagon (1 mg). This was compared with the exocrine pancreatic response to an IV infusion of secretin and cholecystokinin-pancreozymin. Outputs of pancreatic bicarbonate, amylase and trypsin were measured. Exocrine secretory pancreatic function was decreased in 14 patients. Fasting and maximal CPR showed that 9 patients had residual insulin secretion. For these 'CPR-secretors' there was a strong correlation between CPR and output of bicarbonate (r = 0.87, p less than 0.005) and amylase (r = 0.7, p less than 0.05), but not with trypsin. These results suggest the existence of an endocrine-exocrine relationship in the pancreas.
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PMID:The effect of residual insulin secretion on exocrine pancreatic function in juvenile-onset diabetes mellitus. 34 40

The release of enterokinase into human duodenal fluid was studied after intravenous injections of secretin and cholecystokinin-pancreozymin (CCK-PZ). In five control subjects there was a significant release of the enzyme after stimulation with either hormone. A similar release of enterokinase was observed after hormonal stimulation in three patients with total biliary obstruction and in four patients with pancreatic exocrine insufficiency. These results suggest that the hormone-mediated release of enterokinase is independent of bile salts and trypsin in man. This release of enterokinase into duodenal fluid may be physiologically important in protein digestion.
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PMID:The release of enterokinase following secretin and cholecystokinin-pancreozymin in man. 39 1

Precise relationships between pancreatic ductal obstruction and pancreatic secretory capacity have not been established. In this study, we describe the quantitative relationships between the lengths of opacified ducts obtained at retrograde pancreatography and the secretory capcity of the gland for volume, bicarbonate, lipase, and trypsin. Forty-five patients (17 with pancreatic cancer, 6 pancreatitis, 5 other malignancies, and 17 nonmalignant, nonpancreatic disease found at laparotomy) were studied with a method of duodenal intubation and perfusion with basal saline perfusion alone or with continuous intravenous infusion of secretin or of cholecystokinin-pancreozymin. Secretory outputs of volume, bicarbonate, and enzymes compared with the length of opacified ducts showed a significant (P less than 0.05) linear relationship for patients with pancreatic cancer, pancreatitis, and other cancers. The resulting data imply that obstruction of the pancreatic duct is important in decreasing secretion of the pancreas in pancreatic disease. The relationship between obstruction and pancreatic secretion demonstrates that a decrease in exocrine pancreatic secretion cannot be detected until more than 60% of the total length of the main pancreatic duct has been obstructed.
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PMID:The relationships between pancreatic ductal obstruction and pancreatic secretion in man. 43 Nov 21

Investigation of pure human pancreatic juice obtained by direct cannulation of the main pancreatic duct of 11 healthy volunteer subjects and 10 chronic alcoholics without detectable pancreatic disease revealed the presence of numerous acid hydrolases in this secretion. The pH optimal and substrate specificities of these enzymes suggest that they are of lysosomal origin. Stimulation of the pancreas by injection of cholecystokinin-pancreozymin (CCK-PZ) (1 Ivy dog unit/kg) resulted in a striking increase in activity of some of these hydrolases (N-acetyl-beta-D-glucosaminidase, arylsulfatase, etc.) similar to that observed for trypsin, amylase, and other pancreatic digestive enzymes. In a second group of hydrolases (beta-D-glucuronidase, leucine naphthylamidase, etc.) the effect of this hormone was greatly reduced or absent, particularly in normal individuals. In chronic alcoholics enzyme activity in response to CCK-PZ injection was greater than in normal subjects. Although this increase achieved statistical significance (P less than 0.05) in the case of beta-D-glucuronidase only, it was observed for all lysosomal hydrolases tested and suggests either increased synthesis or a more facile release of these enzymes from the pancreas of chronic alcoholics than of normal individuals.
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PMID:Lysosomal enzymes in pure pancreatic juice from normal healthy volunteers and chronic alcoholics. 45 5

The possible role of calcium in human bile during the biliary stimulated exocrine pancreatic secretion was investigated in 15 healthy volunteers. Total outputs of trypsin, bicarbonate, bilirubin and volume in the duodenal juice and serum gastrin were measured during a continuous intravenous infusion of secretion (0.5 CHR U/kg/h) for 40 min. The same parameters were determined after a single intraduodenal dose of Ca++ (20 ml 13,5, 135 or 270 mval/l, n = 5 for each dose) and compared with aequivalent intraduodenal dose of Na+ and an intravenous dose of secretion/cholecystokinin (1 CHR and IDU U/kg). Low calcium (13,5 mval/l) had no effect on the output of pancreatic enzymes and bile. However the higher doses led to a significant increases of the outputs of trypsin and bilirubin, which was about 75% of the enhancement seen with secretin/cholecystokinin in the dose used. Serumgastrin secretion was significantly increased only after the higher calcium doses.--Serum insulin in peripheral venous blood venous blood was unchanged after duodenal application of 20 ml 270 mval/l calcium (n = 5). From these data one has to conclude that the Ca++-content of bile has no stimulatory effect on the exocrine pancreas and on serum gastrin and insulin.
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PMID:[Exocrine pancreatic secretion, gastrin and insulin in men by intraduodenal bolus injection of calcium (author's transl)]. 46 72

The effect of gastric distension on pancreatic secretion of bicarbonate and trypsin was studied in 10 individuals in the basal state or during stimulation with low and high doses of secretin or secretin plus cholecystokinin (CCK). Gastric distension augmented the pancreatic response to secretin but had no consistent effect on the pancreatic response to combination of secretin and CCK. We conclude that gastropancratic reflexes do not have much functional significance in man.
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PMID:Effect of gastric distension on human pancreatic secretion. 48 73

Chronic administration of raw soybean flour containing active trypsin inhibitor to dogs reduced the pancreatic output of trypsin and chymotrypsin in response to cholecystokinin. Dogs stimulated by a meat meal showed no consistent alteration in the output of trypsin and chymotrypsin when given additional duodenal infusions of trypsin and chymotrypsin, or canine pancreatic juice, or ovalbumin trypsin inhibitor. Two dogs, whose pancreas was stimulated by intraduodenal infusion of amino acids, showed no consistent change when trypsin, or trypsin together with trypsin inhibitors, or trypsin together with canine pancreatic juice was infused concurrently into the duodenum. These results indicate that feedback control of pancreatic enzyme secretion, of the type proposed on the basis of studies similar to the present in rats, does not exist in dogs.
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PMID:Chronic and acute studies indicating absence of exocrine pancreatic feedback inhibition in dogs. 56 99


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