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)

The level of adenosine 3':5'-cyclic monophosphate (cAMP) and the activity of adenyl cyclase were studied in the pancreas under normal conditions and during acute hemorrhagic pancreatitis induced by intraductal injection of fresh trypsin-bile-blood mixture. In addition, the adenyl cyclase was localized histochemically in the pancreas. Basal cAMP concentration and adenyl cyclase activity were 0.88 +/- 0.11 pmoles/mg wet tissue and 3.39 +/- 0.21 pmoles/mg protein/min, respectively. The acute pancreatitis drastically reduced the adenyl cyclase activity at 15 minutes to 1.66 +/- 0.54 pmoles/mg protein/min, and totally suppressed adenyl cyclase activity at 30 minutes after the onset of pancreatitis without affecting cAMP levels. The presence of sodium fluoride in the incubation medium prolonged the enzyme activity up to 45 minutes. The progressive disappearance of adenyl cyclase activity presumably resulted from the destruction of cellular integrity caused by autodigestion by the active proteolytic enzymes released during pancreatitis.
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PMID:Adenyl cyclase and cyclic AMP (cAMP) in acute experimental pancreatitis. 18 29

States of hypersecretion of PTH may occur primarily, or in response to other physiologic abnormalities. Primary hyperparathyroidism must be considered in the differential diagnosis of hypercalcemia, nephrolithiasis, metabolic bone disease, and pancreatitis and peptic-ulcer disease. The clinical manifestations of this disease have become more subtle with improved detection. The serum calcium level is almost always elevated, and when it it accompanied by relatively high serum PTH levels or increased urinary cAMP excretion, the diagnosis is usually secure. Findings of hypophosphatemia, decreased renal tubular reabsorption of phosphorus, hypercalciuria, and characteristic roentgenographic changes support the diagnosis of hyperparathyroidism, but are not prerequisites for that diagnosis. Most cases will come to operation, and experienced intraoperative assessment is necessary for the correct distinction between multiglandular disease and that involving only a single gland. We expect that a clearer understanding of the histopathologic features of these diseases, and improvement in the methods for measurement of PTH will be the main areas of advancement in the diagnosis of hyperparathyroidism in the next few years.
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PMID:Diagnosis of hyperparathyroidism. 19 30

Nineteen patients with acute pancreatitis were examined for the activity of LDH, NADH-tetrazolium oxidoreductase, acid phosphatase, the content of calcium salts, cAMP and cGMP in biopsy tissue of the pancreas; pancreatic enzymes and bicarbonates in the duodenal contents and pancreatic juice. The activity of enzymes participating in oxidative metabolism in epithelial cells of the intact pancreas appeared elevated. During the development of destructive changes in the pancreatic parenchyma, the processes of intracellular oxidation get inhibited, the enzymes go out into the intercellular space, calcium transport gets impaired, and acid phosphatase is activated. It has been found that in acute destructive pancreatitis, primarily impaired are epithelial cells of the islets, followed by the impairment of the epithelium of the acini and at the last moment of that of the excretory ducts. The data obtained enable one to regard cyclonucleotides, calcium, pancreatic enzymes and lysosomal hydrolases as pathogenetic elements of acute pancreatitis.
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PMID:[Morphofunctional elements of the pathogenesis of acute pancreatitis]. 164 89

The content of pancreatic enzymes, cyclic nucleotides and prostaglandins (PG) in the duodenal contents was measured in 77 patients with chronic pancreatitis and in 20 healthy individuals. Pancreatitis exacerbation was attended by a decrease in enzymatic activity, in bicarbonate, cAMP and cGMP production. The content of PGE in pancreatic secretion remained normal, that of PGF2 alpha was elevated. Stimulation of the exocrine part of the pancreas by means of euphylline, pentagastrin and calcium was accompanied by the rise of the content of cyclic nucleotides rather than of PG. Suppression of enzymatic secretion by contrykal was followed by the reduction in the content of the cyclic nucleotides and PGE. The data suggest that cyclic nucleotides and PG are involved in the mechanism by which the external secretion of the pancreas is impaired in patients with chronic pancreatitis.
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PMID:[Prostaglandins and cyclic nucleotides in chronic pancreatitis]. 247 Dec 85

The rate of protein phosphorylation, as catalyzed by the protein kinase enzymes, was measured in the pancreas of rats with acute experimental pancreatitis. Two different methods were used to induce pancreatitis in rats: retrograde injection of deoxycholate (DOC) into the pancreatic duct, or daily intravenous administration of DL-ethionine. Basal protein kinase activity was elevated in rats with acute experimental pancreatitis. This increase in activity was not dependent on free Ca2+ and did not result from elevated cAMP levels. To assess the possible role of digestive enzymes in protein kinase activation, tissue extracts from healthy controls were subjected to mild treatment with digestive enzymes and DOC. Trypsin, chymotrypsin, phospholipase A, and DOC produced protein kinase activation of a similar magnitude as found in diseased tissue. Results indicate that stimulated protein kinase activity in tissue of animals with acute pancreatitis may arise from the action of digestive enzymes.
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PMID:Stimulated protein kinase activity during acute pancreatitis in rats. Possible mediation by proteolysis, lipolysis, and bile salts. 402 26

Patients with chronic recurrent pancreatitis were examined for the blood content of insulin, glucagon, somatostatin (SS), somatotropin (STH), cAMP and cGMP. The blood content of insulin, glucagon and STH was normal, that of SS and cAMP elevated, and that of cGMP lowered. In severe pancreatitis, the endocrine part of the pancreas was activated. The relationship was established between the level of amylasemia and the activity of islet cells and the blood content of cGMP. The compensatory importance of hypersecretion of SS and glucagon for pancreatitis exacerbation is demonstrated. The role of cyclic nucleotides in the pancreatic activity is discussed.
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PMID:[Pancreatic hormones and cyclic nucleotides in the blood in chronic recurrent pancreatitis]. 615 52

The balance between the concentrations of free ionized Ca2+ and bicarbonate in pancreatic juice is of critical importance in preventing the formation of calcium carbonate stones. How the pancreas regulates the ionic composition and the level of Ca2+ saturation in an alkaline environment such as the pancreatic juice is not known. Because of the tight cause-effect relationship between Ca2+ concentration and lithogenicity, and because hypercalcemia is proposed as an etiologic factor for several pancreatic diseases, we have investigated whether pancreatic tissues express a Ca2+-sensing receptor (CaR) similar to that recently identified in parathyroid tissue. Using reverse transcriptase-polymerase chain reaction and immunofluorescence microscopy, we demonstrate the presence of a CaR-like molecule in rat pancreatic acinar cells, pancreatic ducts, and islets of Langerhans. Functional studies, in which intracellular free Ca2+ concentration was measured in isolated acinar cells and interlobular ducts, show that both cell types are responsive to the CaR agonist gadolinium (Gd3+) and to changes in extracellular Ca2+ concentration. We also assessed the effects of CaR stimulation on physiological HCO3- secretion from ducts by making measurements of intracellular pH. Luminal Gd3+ is a potent stimulus for HCO3- secretion, being equally as effective as raising intracellular cAMP with forskolin. These results suggest that the CaR in the exocrine pancreas monitors the Ca2+ concentration in the pancreatic juice, and might therefore be involved in regulating the level of Ca2+ in the lumen, both under basal conditions and during hormonal stimulation. The failure of this mechanism might lead to pancreatic stone formation and even to pancreatitis.
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PMID:Molecular and functional identification of a Ca2+ (polyvalent cation)-sensing receptor in rat pancreas. 1040 Jun 86

Cystic fibrosis (CF) is caused by mutations in the CF transmembrane conductance regulator (CFTR) gene which encodes a protein expressed in the apical membrane of exocrine epithelial cells. CFTR functions principally as a cAMP-induced chloride channel and appears capable of regulating other ion channels. Besides the most common mutation, DeltaF508, accounting for about 70% of CF chromosomes worldwide, more than 850 mutant alleles have been reported to the CF Genetic Analysis Consortium. These mutations affect CFTR through a variety of molecular mechanisms which can produce little or no functional CFTR at the apical membrane. This genotypic variation provides a rationale for phenotypic effects of the specific mutations. The extent to which various CFTR alleles contribute to clinical variation in CF is evaluated by genotype-phenotype studies. These demonstrated that the degree of correlation between CFTR genotype and CF phenotype varies between its clinical components and is highest for the pancreatic status and lowest for pulmonary disease. The poor correlation between CFTR genotype and severity of lung disease strongly suggests an influence of environmental and secondary genetic factors (CF modifiers). Several candidate genes related to innate and adaptive immune response have been implicated as pulmonary CF modifiers. In addition, the presence of a genetic CF modifier for meconium ileus has been demonstrated on human chromosome 19q13.2. The phenotypic spectrum associated with mutations in the CFTR gene extends beyond the classically defined CF. Besides patients with atypical CF, there are large numbers of so-called monosymptomatic diseases such as various forms of obstructive azoospermia, idiopathic pancreatitis or disseminated bronchiectasis associated with CFTR mutations uncharacteristic for CF. The composition, frequency and type of CFTR mutations/variants parallel the spectrum of CFTR-associated phenotypes, from classic CF to mild monosymptomatic presentations. Expansion of the spectrum of disease associated with the CFTR mutant genes creates a need for revision of the diagnostic criteria for CF and a dilemma for setting nosologic boundaries between CF and other diseases with CFTR etiology.
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PMID:Genotype and phenotype in cystic fibrosis. 1077 83

Transcript levels of the human serine/threonine kinase h-sgk have been found to be highest in pancreas. In the present study, localization and regulation of h-sgk transcription in pancreatic tissue were elucidated. As was apparent from radioactive in situ hybridization, most pancreatic acinar cells expressed high levels of h-sgk mRNA. h-sgk mRNA-positive cells were also found in ductal epithelia but not in pancreatic islets. In biopsy specimens from patients with pancreatitis, h-sgk mRNA levels were decreased in acinar cells but abundant in numerous mononuclear interstitial cells within areas of pancreatic necrosis and fibrosis. As shown by Northern blotting, h-sgk transcription in DAN-G pancreatic tumor cells is upregulated by osmotic cell shrinkage, serum, phorbol esters (phorbol 12,13-didecanoate), and Ca(2+) ionophore A-23187 and decreased by staurosporine and cAMP. In conclusion, h-sgk transcription is regulated not only by cell volume but also by serum, protein kinase C stimulation, cAMP, and increase of intracellular Ca(2+) activity. The kinase may participate not only in normal function of exocrine pancreas but also in fibrosing pancreatitis.
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PMID:Expression of cell volume-regulated kinase h-sgk in pancreatic tissue. 1105 97

Prostaglandin E(2) (PGE(2)) inhibits pancreatic enzyme secretion and shows a protective action against pancreatitis. In this study, we tested the effects of PGE(2) on the slowly activating voltage-dependent K(+) channel current ( I(Ks)) and cholecystokinin (CCK)-induced oscillations of cytosolic [Ca(2+)] ([Ca(2+)](i)) in rat pancreatic acini (RPA). I(Ks) in RPA is reportedly augmented by both Ca(2+)- and cAMP-mediated secretagogues. PGE(2) (10(-7) M) decreased the amplitude of I(Ks), an effect that was more prominent following prior stimulation with secretin. The application of the membrane-permeable cAMP analogue 8-Br-cAMP prevented the effect of PGE(2) on I(Ks). The Ca(2+)-mediated augmentation of I(Ks) by ACh was unaffected by pretreatment with PGE(2). Using fura-2 fluorescence ratiometry to assess [Ca(2+)](i), CCK (<or=10(-10) M)-induced Ca(2+) oscillations were observed in RPAs. The amplitude of the Ca(2+) oscillations was decreased by PGE(2), irrespective of the presence of 8-Br-cAMP. RT-PCR analysis showed that RPAs express predominantly the EP3 subtype of the PGE(2) receptor and its splice variants. Enzyme-immunoassay showed that the secretin-induced production of cAMP in RPAs was inhibited by treatment with PGE(2). In summary, PGE(2) acts on the EP3 receptors to antagonize the cAMP-generating effect of secretin, resulting in the decrease of I(Ks). In addition, PGE(2) suppresses CCK-induced Ca(2+) oscillations in a cAMP-independent manner. These effects of PGE(2) may explain the inhibitory action mechanism of PGE(2) in the exocrine pancreas.
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PMID:Inhibitory effects of PGE(2) on K(+) currents and Ca(2+) oscillations in rat pancreatic acinar cells. 1219 15


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