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)

Islets of Langerhans were isolated from mouse pancreases and fixed in periodatelysine-paraformaldehyde. The fixed islets were then dissociated with trypsin and EDTA to yield cell suspensions that contained mainly four cell types; beta-cells, capillary endothelial cells, acinar cells, and pancreatic duct epithelial cells. The nonislet cells were probably associated wtih the surface of the isolated islets. The H-2 antigens of the dissociated pancreatic cells were labeled with an immunoferritin technique. Pancreatic duct epithelial cells showed specific ferritin labeling on their lateral cell membranes but not on apical microvillus membranes. Acinar cells were also labeled on lateral membranes, and the capillary endothelial cells were labeled on both the luminal and albuminal aspects of their surface membranes. In contrast, pancreatic beta-cells were unlabeled. The number of ferritin molecules per unit length of beta-cell membrane was essentially the same on cells from the antigenic strain and the congeneic control strain, and was about 200-fold less than on the labeled pancreatic duct epithelial cell lateral membranes. Pancreatic beta-cells are therefore one of six known epithelial cell types on which H-2 antigens can not be detected by immunoferritin labeling. The apparent absence of H-2 antigens from these cells suggests a study of the viability of beta-cells in allografts of dissociated islet cells, in which the beta-cell would not be in contact with antigenic cells. Such studies might lead to a new approach to the control of diabetes mellitus by transplantation.
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PMID:The absence of H-2 antigens from mouse pancreatic beta-cells demonstrated by immunoferritin labeling. 10 71

The pathogenesis of endoscopic retrograde cholangiopancreatography (ERCP)-induced pancreatitis is poorly understood. To elucidate a role for pancreatic enzymes in ERCP-induced pancreatitis, we measured serum amylase, lipase, trypsin, and elastase in 25 patients undergoing ERCP. Serum alpha 1-antitrypsin and alpha 2-macroglobulin, two major pancreatic protease inhibitors, also were measured. All pancreatic enzymes measured rose significantly after ERCP. Pancreatic duct cannulation was associated with a greater elevation in serum amylase and lipase. Circulating alpha 2-macroglobulin was reduced by 7% (p = 0.04) 6 h after ERCP, whereas circulating alpha 1-antitrypsin increased over the same time period. Papillotomy, stent placement, or underlying disease did not influence changes any further. Three patients developed ERCP-induced pancreatitis. All three patients had circulating alpha 2-macroglobulin levels below 243 mg/dl (p = 0.03). The ERCP-induced alterations in circulating pancreatic enzymes and their inhibitors are similar to changes seen in clinical pancreatitis. Low circulating alpha 2-macroglobulin levels may predispose to ERCP-induced pancreatitis.
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PMID:The effect of ERCP on circulating pancreatic enzymes and pancreatic protease inhibitors. 171 6

Canine and human exocrine pancreatic secretion into the duodenum during fasting is cyclical and related to intestinal motility. To characterize the composition of pure pancreatic juice during the cyclically recurring sequence of propagated motor events (interdigestive motor complex) and to establish whether pancreatic reflux occurs, dogs were prepared with three permanent indwelling duodenal catheters and a pancreatodochal cutaneous catheter. The duodenal catheters were used to record duodenal pressures and measure pancreatic secretion of trypsin, lipase, and bicarbonate, based on the recovery of a constantly perfused marker, [14C]PEG. Pancreatic duct pressures or pancreatic juice concentrations of [14C]PEG, trypsin, lipase, or bicarbonate (done separately in each of five dogs throughout one interdigestive cycle on 4 different days) were related to duodenal motor activity. Finally, the pancreatic duct orifice of freshly sacrificed dogs was examined by light and electron microscopy. During fasting, (1) pancreatic volume secretion increased 10-fold during phases II, III, and IV (P less than 0.001), and bicarbonate concentration increased during phases III and IV (P less than 0.05) compared with phase I, while trypsin and lipase concentrations did not change; (2) reflux of duodenally perfused [14C]PEG into the pancreatic duct occurred in two of five dogs and was minimal (less than 0.1%); and (3) a positive mean pressure gradient from duodenum to pancreatic duct occurred only during phase III (7.4 +/- 4.1 cm H2O). Anatomic studies of the pancreatic duct opening showed a specialized papillary mucosa and an independent crescentic sphincter muscle. We conclude that during fasting, pancreatic juice composition is intimately linked to the different phases of interdigestive intestinal motor activity and that an efficient antireflux mechanism exists.
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PMID:Interdigestive canine pancreatic juice composition and pancreatic reflux and pancreatic sphincter anatomy. 724 90

Pancreatic duct cells secrete bicarbonate-rich fluids, which are important for maintaining the patency of pancreatic ductal trees as well as intestinal digestive function. The bulk of bicarbonate secretion in the luminal membrane of duct cells is mediated by a Cl(-)-dependent mechanism (Cl(-)/HCO(3)(-) exchange), and we previously reported that the mechanism is CFTR-dependent and cAMP-activated (Lee, M. G., Choi, J. Y., Luo, X., Strickland, E., Thomas, P. J., and Muallem, S. (1999) J. Biol. Chem. 274, 14670-14677). In the present study, we provide comprehensive evidence that calcium signaling also activates the same CFTR- and Cl(-)-dependent HCO(3)(-) transport. ATP and trypsin evoked intracellular calcium signaling in pancreatic duct-derived cells through the activation of purinergic and protease-activated receptors, respectively. Cl(-)/HCO(3)(-) exchange activity was measured by recording pH(i) in response to [Cl(-)](o) changes of the perfusate. In perfusate containing high concentrations of K(+), which blocks Cl(-) movement through electrogenic or K(+)-coupled pathways, ATP and trypsin highly stimulated luminal Cl(-)/HCO(3)(-) exchange activity in CAPAN-1 cells expressing wild-type CFTR, but not in CFPAC-1 cells that have defective (DeltaF508) CFTR. Notably, adenoviral transfection of wild-type CFTR in CFPAC-1 cells completely restored the stimulatory effect of ATP on luminal Cl(-)/HCO(3)(-) exchange. In addition, the chelation of intracellular calcium by 1,2-bis(2-aminophenoxy)ethane-N,N,N,N'-tetraacetic acid (BAPTA) treatment abolished the effect of calcium agonists on luminal Cl(-)/HCO(3)(-) exchange. These results provide a molecular basis for calcium-induced bicarbonate secretion in pancreatic duct cells and highlight the importance of CFTR in epithelial bicarbonate secretion induced by various stimuli.
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PMID:Ca2+ activates cystic fibrosis transmembrane conductance regulator- and Cl- -dependent HCO3 transport in pancreatic duct cells. 1240 1

In humans, pancreatic hyperechogenicity and duct dilation are reported as normal aging changes. Similar changes have been reported with pancreatitis in the cat. We attempted to determine if aging changes occur in the ultrasound appearance of the normal feline pancreas. The pancreas of 84 normal (based on history, physical exam, biochemical profile, and feline trypsin-like immunoreactivity and pancreatic lipase immunoreactivity concentrations) cats of varying ages was scanned. Pancreatic width at the left limb and body, pancreatic duct diameter at left limb and body, and pancreatic echogenicity compared with liver and surrounding fat were noted and compared with age and body weight. Lower and upper limits of the 95% reference intervals for pancreatic left limb width were 2.6 and 9.5 mm, and 3.5 and 8.5 mm for the pancreatic body width. There was no significant difference in pancreatic width between the left limb and body. Lower and upper limits of the 95% reference interval for the diameter of the pancreatic duct at the left limb and body were similar, and were 0.65 and 2.5 mm. There was a weak but significant linear correlation between pancreatic duct diameter and age, with increasing pancreatic duct diameter with increasing age. There was no correlation of pancreatic width with age, and no correlation of pancreatic echogenicity with age or body weight. Based on this study, feline pancreatic size and echogenicity do not change with age. Pancreatic duct diameter increases slightly with age and should not be used as a sole indicator of pancreatitis in the geriatric cat.
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PMID:Age-relatedchanges in the ultrasound appearance of the normal feline pancreas. 1605 Feb 83