Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0030305 (pancreatitis)
 16,014 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Somatostatin is an inhibitory hormone that decreases the secretion and end organ response of cholecystokinin (CCK). Inhibition of hormonal stimulation of pancreatic exocrine secretion by somatostatin may improve the course of acute pancreatitis. Anesthetized dogs underwent cholecystectomy and cannulation of the pancreatic duct, thoracic duct, and portal vein. Twenty experiments were performed in random order with 5 dogs in each group. Hourly measurements of lymph flow and portal and thoracic duct amylase were made. Portal blood insulin, glucagon, and CCK concentrations were determined by radioimmunoassay on samples obtained at the beginning and end of the experiments. Pancreatitis was induced by injecting, under constant pressure, 10 ml bile into the pancreatic duct during 1 min. Somatostatin was administered intravenously (20 micrograms/kg/hr). After 5 h, the dogs were killed, pancreas glands removed and weighed and tissue samples obtained for histologic evaluation. There was a significant increase in lymph amylase output and portal venous amylase and CCK concentrations in the dogs with pancreatitis compared to the control dogs. In dogs with pancreatitis, lymphatic amylase secretion and portal CCK concentrations were significantly decreased by somatostatin. Somatostatin did not significantly alter portal amylase concentrations, pancreas gland weights or histologic inflammation when compared to values from dogs with pancreatitis not treated with somatostatin.
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PMID:Effects of somatostatin on acute canine experimental pancreatitis. 244 77

Organophosphates (OPs) cause irreversible inhibition of cholinesterases (ChEs) and profound cholinergic stimulation. There are major differences in the response of the dog and cat pancreas to the in vivo administration of Diazinon (O,O-diethyl O-2-isopropyl-4-methyl-6-pyrimidyl phosphothioate), a butyrylcholinesterase (BuChE) inhibitor. Acute edematous pancreatitis is found in the dog but not in the cat. The present experiments were designed to see what effect OP had in vitro on pancreatic exocrine function of dog, cat, and guinea pig, and whether the effects were consistent with an anti-ChE activity. A water-soluble OP agent, tetraisopropyl pyrophosphoramide (iso-OMPA) at 10(-3) M, which like Diazinon inhibits BuChE, was used. Minced pieces of fresh whole pancreata 3 mm in size were taken from 3 dogs, 4 guinea pigs, and 2 cats. The tissues were placed in flasks containing Eagle's solution and gassed with 100% O2. Cumulative amylase release was measured by Phadebas method up to 3 h. At half-maximal acetylcholine (ACH) concentration (10(-5) M), the canine pancreas pretreated with iso-OMPA (10(-3) M) showed a 42-87% greater release of amylase than tissues receiving ACH alone (p less than 0.001). The same potentiated response to ACH was seen in guinea pig pancreas pretreated with iso-OMPA (p less than 0.001), but iso-OMPA pretreatment did not augment the ACH response in the cat. Atropine pretreatment effectively blocked all ACH responses, and there was no effect seen with iso-OMPA alone. In the dog, iso-OMPA in combination with half-maximal carbachol (10(-6) M), or in combination with half-maximal cholecystokinin (CCK-8) stimulation (10(-9) M), provided no potentiated amylase release.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of the organophosphate iso-OMPA on amylase release by pancreatic lobules of dog, guinea pig, and cat. 244 88

Rats with acute experimental pancreatitis were treated with the cholecystokinin (CCK)-receptor antagonist proglumide. S-amylase was not affected by proglumide during the initial 4 h but was reduced after 72 h as compared to pre-pancreatitis values. The amylase levels in peritoneal fluid were lower in proglumide treated animals at 1, 2, 4 and 72 h after the induction of the pancreatitis, and amylase in pancreatic tissue was increased by proglumide after six but not 72 h. In spite of these biochemical changes, suggesting beneficial therapeutic effects by proglumide, survival rate was not improved when using a dose of 100 mg/kg every 8 h for 48 h and significantly reduced at a dose of 500 mg/kg every 8 h for 48 h. The results do not support proglumide as the sole treatment in acute pancreatitis.
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PMID:Proglumide treatment in bile-induced acute experimental pancreatitis. 245 22

We have examined the possibility that the 33- and 39-amino acid forms of cholecystokinin (CCK) are cleaved to produce CCK-octapeptide (CCK-8) during circulation in humans. When a mixture of the 33- and 39-amino acid forms of porcine CCK was infused at 0.1-2.5 pmol/kg.min into normal subjects, material indistinguishable from CCK-8 by gel filtration and in region-specific radioimmunoassays appeared in plasma, together with an intermediate form that eluted between the 33- and 8-amino acid peptides. During infusions, plasma concentrations of CCK-33/39, CCK-8, and the intermediate CCK rose to 63 +/- 26 (mean +/- SE), 57 +/- 12, and 18 +/- 10 pmol/L, respectively. Cholecystokinin-octapeptide appeared rapidly and constituted approximately 40% of total CCK-like immunoreactivity after 5 min of infusion. Octapeptide-like material also appeared, but at a slower rate, when CCK-33 was incubated at 37 degrees C with human plasma. Thus after 5 min, and throughout the incubation, CCK-8 comprised approximately 20% and CCK-33 approximately 75% of total immunoreactivity. Cholecystokinin-33 disappeared more rapidly and small forms appeared in higher concentrations in plasma from patients with acute pancreatitis. Thus, after incubation for 120 min, CCK-33 and CCK-8 comprised 45% +/- 7% and 13% +/- 3% of initial immunoreactivity in normal plasma, but 18% +/- 6% and 33% +/- 9%, respectively, in plasma from patients with pancreatitis. Ethylenediaminetetraacetic acid, but not aprotinin, inhibited the cleavage of CCK-33 to produce CCK-8, and the degradation of CCK-8 in normal plasma in vitro.
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PMID:Cholecystokinin cleavage to cholecystokinin-octapeptide in vivo and in vitro: accelerated cleavage in acute pancreatitis. 245 90

Asperlicin (ASP), a new, nonpeptidal cholecystokinin (CCK) receptor antagonist isolated from the fungus Aspergillus alliaceus, has an affinity that is 300-400 times greater than that of proglumide for gallbladder, ileal, and pancreatic CCK receptors. The long in vivo half-life and high selectivity for peripheral CCK receptors make ASP suitable for investigations on the physiological and pharmacological actions of CCK. Endogenous CCK has been postulated to participate in the pathogenesis of acute hemorrhagic pancreatitis (AHP) in rats and mice. We examined the effects of ASP in rats on the early course (6 h) of AHP induced by a retrograde infusion of sodium taurocholate (NaTC) into the common bile-pancreatic duct. An i.v. bolus injection of ASP (either 10 mg/kg or 30 mg/kg) in dimethyl sulfoxide (DMSO) given 1 h prior to AHP induction failed to significantly alter pancreas weights, serum amylase concentrations, or pancreatic histopathology when compared with AHP control rats treated with vehicle alone. However, rats given 2 i.p. injections of ASP (either 20 mg/kg/injection or 40 mg/kg/injection) in DMSO: olive oil 1 h before and 2 h after induction of AHP exhibited significantly reduced serum amylase concentrations. Additionally, rats given the high dose i.p. injections of ASP also had significantly reduced pancreas weights and less severe pancreas histopathology compared with AHP control animals. These data indicate that endogenous CCK participates in the pathogenesis of NaTC-induced AHP in the rat.
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PMID:Asperlicin, a nonpeptidal cholecystokinin receptor antagonist, attenuates sodium taurocholate-induced acute pancreatitis in rats. 245 74

This study describes the effect on the function and structure of the saline-perfused cat pancreas of factors implicated in the pathogenesis of pancreatitis (bile acid, ethanol, pancreatic enzymes) after their addition to the perfusion fluid or their instillation into the pancreatic duct. Instillation of trypsin or chenodeoxycholic acid, but not ethanol, into the pancreatic duct resulted in a profound suppression of secretory function. The leakage of perfusion fluid and amylase from the gland was also abruptly increased. Intraarterial perfusion of trypsin also inhibited secretin-induced flow and cholecystokinin evoked enzyme secretion. Intraarterial bile acid inhibited fluid flow but augmented enzyme secretion in a concentration-dependent manner. In addition, massive or focal parenchymal necrosis was caused by sustained intraarterial perfusion of bile acid or trypsin, respectively. Elastase and phospholipase A had little influence on pancreatic function or structure when added to the perfusion fluid. These findings show that pancreatic structure and function can be disturbed by potentially toxic factors administered not only via the ductal system but also via the vascular route, and consequently suggest that an "internal reflux" mechanism could be involved in the pathogenesis of pancreatitis in addition to a "ductal reflux" mechanism.
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PMID:Analysis in the isolated perfused cat pancreas of factors implicated in the pathogenesis of pancreatitis. 245 94

Cholecystokinin (CCK) has been suggested to be involved in the pathogenesis of acute pancreatitis. To test this hypothesis, we administered the highly selective and specific CCK receptor antagonist L 364,718 to rats in which acute experimental pancreatitis had been induced by the use of transduodenal pancreatic duct injection of taurocholate. It was, however, found that despite the use of L 364,718 at a high dose level (1 mg/kg body weight given three times), and also given prior to induction of pancreatitis, the mortality rate, the serum or ascites amylase activity, the pancreatic concentrations of lysosomal enzymes or the morphology of the pancreas were not affected. This suggests that the CCK receptors are not involved in the pathogenesis of acute pancreatitis in this experimental model, and, consequently, that CCK receptor antagonists have no place in the therapy of this condition.
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PMID:Effects of the specific cholecystokinin antagonist L 364,718 in experimental acute pancreatitis in the rat. 246 58

The nude mouse has been used to evaluate the effect of cholecystokinin (CCK) on xenografted tissues, but little is known about long-term actions of cholecystokinin on native organs in this animal. We investigated the impact of chronically administered synthetic cholecystokinin octapeptide on the nude mouse. Six groups of eight animals each received intraperitoneal injections twice daily for 14 days with diluent or a 4-log range of cholecystokinin. Overall health, behavior, and body weight were unaffected by this treatment. Among the seven organs examined at necropsy, pancreas alone showed a dose-related increase in weight. Pancreatic DNA content decreased with increasing dosages of CCK-8, while RNA content exhibited a biphasic response to CCK-8. The only histological abnormality occurred in the pancreas and was confined to the higher doses. These data indicate for the first time the action of CCK on the non-tumor-bearing nude mouse. Unlike other animal models, the nude mouse responds to cholecystokinin administration with pancreatic hypoplasia and hypertrophy, which is accompanied by pancreatitis at higher doses.
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PMID:Effect of chronically administered cholecystokinin on the nude mouse. 246 35

The management of acute pancreatitis has not changed appreciably throughout several decades. Recent evidence has suggested that cholecystokinin (CCK) may play an important role in pancreatic disease. Investigations into the precise role of CCK in acute pancreatitis have been hampered by the lack of a specific CCK receptor antagonist. Using a newly described, highly potent and specific CCK receptor antagonist, L-364,718, the effect of CCK in two models of acute "surgical" pancreatitis was examined: (1) the bile salt ductal perfusion model in the rat and (2) a traumatic model in the guinea pig. At a suboptimal dose for pancreatic enzyme secretion (25 pmol/kg/h), CCK was found to potentiate the severity of the ensuing pancreatitis in both models. Continuous CCK receptor blockade with L-364,718 (25 nmol/kg/h) improved biochemical, morphologic, and survival indexes. This study suggests that physiologic levels of CCK play an important permissive role in the evolution of acute pancreatitis. The use of L-364,718 as an investigative probe or therapeutic tool for acute pancreatitis is worthy of further consideration.
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PMID:Cholecystokinin augmentation of 'surgical' pancreatitis. Benefits of receptor blockade. 246 10

Acute edematous pancreatitis was produced in rats by subcutaneous administration of caerulein. Pancreas weight, pancreas histology and plasma amylase were used as endpoints to quantitate the severity of the syndrome. A caerulein dose of 10 micrograms/kg.hour produced the most severe pancreatitis, whereas at 5 micrograms/kg.hour the values were half-maximal. The pancreatic lesions were characterized by edema, formation of cytoplasmic vacuoles, leukocytic infiltration, necrosis, and with time (12-hour caerulein infusion) dilated acini. Cholecystokinin octapeptide also produced pancreatitis when given at ten times the dose required for caerulein (50 micrograms/kg.hour instead of 5 micrograms/kg.hour). Carbachol did not induce pancreatitis. Two prostaglandins, 16,16-dimethyl prostaglandin E2 injected subcutaneously and prostaglandin E2 infused subcutaneously, dose dependently prevented caerulein-induced pancreatitis (pancreatic edema, leukocytic infiltration, and necrosis) and reduced the number and size of intracellular vacuoles. The ED50 were 15 to 25 micrograms/kg for 16,16-dimethyl prostaglandin E2 and 90 micrograms/kg.hour for prostaglandin E2. Neither prostaglandin, given at doses inhibiting the development of pancreatitis, prevented the retardation of gastric emptying caused by caerulein, a finding suggesting that the prostaglandins may act specifically on the effect of caerulein on the pancreas but not on caerulein receptors in gastric smooth muscle. Indomethacin, an inhibitor of prostaglandin synthesis, and methscopolamine bromide, an anticholinergic agent, had no effect on caerulein-induced pancreatitis. We concluded that prostaglandins of the E type prevent the development of caerulein-induced pancreatitis. The mechanism by which prostaglandins protect the pancreas may involve stabilization of lysosomes within the acinar cells and inhibition of intracellular activation of pancreatic digestive enzymes.
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PMID:Prevention by prostaglandins of caerulein-induced pancreatitis in rats. 246 59


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