Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A highly sensitive and specific radioimmunoassay for somatostatin has been used to study inactivation of the neurohormone by plasma and hypothalamic peptidase(s). Specificity of the inactivation process was indicated by the absence of interference by addition of luteinizing hormone releasing hormone, thyrotropin-releasing hormone, oxytocin, or substance P. The inactivating ability of hypothalamic tissue and plasma was destroyed by heating and the protease inhibitor benzamidine prevented plasma activity, thus suggesting the enzymatic nature of the processes involved. The present data suggest that the inactivation of somatostatin by hypothalamus and plasma could be an important factor in the regulation of circulating somatostatin levels.
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PMID:Enzymatic degradation of somatostatin by rat plasma and hypothalamus. 70 24

From rat brain, a membrane bound substance P-degrading endopeptidase (SPE) was purified 1580 fold to near homogeneity. After extraction with 10 mM CHAPS, the enzyme preparation was subjected to ion exchange chromatography on DEAE-cellulose, adsorption chromatography on hydroxyapatite, gelfiltration through Ultrogel AcA 44 and FPLC on Mono Q. This enzyme of 70,000 molecular weight is optimally active at pH 7.5. Metal chelators (EDTA and EGTA) and sulfhydryl modifying reagents (N-ethylmaleimide and p-chloromercuriphenylsulfonic acid) are strongly inhibitory while the serine-protease inhibitor diisopropyl-fluorophosphate does not effect the enzyme activity. The enzyme is strongly inhibited by bacitracin but not by phosphoramidon and captopril. Degradation of substance P is strongly inhibited by neurotensin, somatostatin, ACTH 1-39, and less effectively by LHRH but not by Leucine-enkephalin. Substance P is preferentially hydrolyzed at the Gln6-Phe7 peptide bond but fragmentation at the Pro4-Gln5, Gln5-Gln6,Phe7-Phe8 and Gly9-Leu10 bonds was also observed.
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PMID:A membrane bound substance P degrading endopeptidase from rat brain. 244 28

The regulation of rainbow trout prolactin (PRL) cells has been investigated. (PRL) cell activity was assessed using acid gel electrophoresis to measure PRL release in vitro and image analysis to measure PRL cell nuclear area, an index of synthetic activity. Somatostatin (SRIF) reduced PRL release during a 3-hr incubation, but not during 18 hr unless the protease inhibitor, bacitracin, was included in the medium. Synthesis during 18 hr was inhibited by SRIF, an effect also enhanced by bacitracin. The effect of SRIF appears to be relatively short-lived, presumably due to proteolytic degradation. The SRIF antagonist cyclo[7-aminohepatanoyl-Phe-D-Trp-Lys-Thr(BZL)] blocked the inhibitory effect of SRIF. A 48-hr pretreatment with 17 beta-oestradiol to stimulate PRL cell activity did not prevent the inhibitory effects of SRIF, rather the response was enhanced. This evidence further supports a role for SRIF in regulation of rainbow trout PRL secretion.
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PMID:The regulation of prolactin cells in the rainbow trout (Oncorhynchus mykiss). 2. Somatostatin. 791 Aug 4

It is known that proteases participate in cellular protein turnover and eliminate abnormal and potentially toxic proteins. Disturbed proteolysis may be responsible for generating the pathological features of some neurodegenerative disorders. Alzheimer disease, for instance, is the most common neurodegenerative disorder and a condition in which proteins of the cell membrane and cytoskeleton are abnormally processed and accumulated in the brain. It is of interest to investigate the effect of protease inhibitors on neurons and neurotransmitter systems in the brain. We examined neurochemical and morphological neuronal changes in the rat brain following long-term intracerebroventricular infusion of leupeptin, a potent calcium-activated protease (calpain) inhibitor. Leupeptin (5 mg) was infused into the lateral ventricle using an osmotic minipump for 14 days. We found a significant reduction of regional choline acetyltransferase activities in the hippocampus, and of somatostatin concentrations in the hypothalamus and entorhinal cortex. Moreover, leupeptin caused a wide-spread, highly significant decrease in neuropeptide-Y concentrations. Leupeptin infusion produced severe degeneration of neuronal processes in both axons and dendrites, and accumulation of electron-dense bodies in the hippocampus. The results indicate that long-term intracerebroventricular infusion of leupeptin in the rat produces neurochemical and morphological changes resembling those of some neurodegenerative disease and aging. Abnormal proteolysis caused by either reduced protease or enhanced protease inhibitor activities might play an important role in these conditions.
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PMID:Neurochemical and pathological alterations following infusion of leupeptin, a protease inhibitor, into the rat brain. 887 12

Morphological and physiological adaptation in residual small intestine occurs after massive enterectomy and is influenced significantly by different growth factors and hormones. The mechanism of adaptation occurs through hypertrophy and hyperplasia as well as nutrient transporter changes. These transporters are classified into different classes dependent on its biological properties. The adaptation process evolves over time and different nutrient absorption profiles occur at different postoperative stages. There is an initial decrease in amino acid transport after resection followed by a return to approximately normal levels. Glucose also follows a similar pattern of changes but returns to normal later than amino acids. The time course of these changes are different for different animals with rat adaptation being much faster than rabbit. Growth hormone (GH) induces increased amino acid transport during this adaptation period, however, appears not to affect small intestine hypertrophy or hyperplasia. The increase in transport occurs via an increase in transport numbers rather than affinity. Epidermal growth factor (EGF) also increases amino acid transport in postoperative animals. Its advantage is it is orally stable when given with a protease inhibitor. EGF also reverses the down-regulating effects of the somatostatin analogue Octreotide (SMS) post resection. EGF in combination with GH has additive effects. However, the effects of the growth factors are site specific. GH and EGF combination therapy significantly increased alanine and arginine transport in distal small bowel after 70 % enterectomy but not in the proximal small bowel. The same combination increases leucine and glutamine transport in the proximal small intestine only. Understanding the specific changes that occur with these therapies may improve quality of life for patients and also reduce that need for total parenteral nutrition.
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PMID:Intestinal adaptation and amino acid transport following massive enterectomy. 934 74

The mortality rate in acute pancreatitis (AP) is significantly lower in patients hospitalized directly at the intensive care unit than in patients admitted to hospital in 2 weeks after the assessment of diagnosis, prophylactic administration of low-molecular protease inhibitor reduces the occurrence of post ERCP pancreatitis a well a coincident complications. Despite rational considerations concerning the significance of pryphylactic administration of antibodies (ATB) in severe AP, there still not enough convincing data which could be recommended a standard therapy. One of the concepts of causal therapy of AP. Suggest that inhibition of exocrine pancreatic enzymatic secretion reduces autodigestion of the gland (setting the gland at rest). The reports on success of secretin-inhibiting substances a glucagon, calcitonin, atropine and somatostatin require confirmation in randomized or accurately defined comparable groups. The initial studies on the therapeutic significance of lexipanphate-antagonist of platelet activating factor (PAF) in acute pancreatitis is promising. A long-term lavage had reduced the mortality.
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PMID:[Therapy of acute pancreatitis]. 972 66

A pancreaticopleural effusion is a rare complication of chronic pancreatitis. Fasting, a protease inhibitor, and/or a surgical intervention are generally selected for the treatment of the pancreatic effusion. We reported here the case, in which octreotide acetate was effective for resolving pancreatic effusion. A 67-year-old man was admitted with a massive pleural effusion. This effusion contained a high level of amylase. Endoscopic retrograde pancreatography followed by computed tomography revealed a pancreaticopleural fistula. The pleural effusion was not improved by the treatment of the protease inhibitor with total parenteral nutrition and fasting. A pancreatic stent could not be emplaced because the major pancreatic duct was coiled. Administration of octreotide acetate, a long-acting somatostatin analogue, markedly diminished the effusion and closed the pancreaticopleural fistula. Transient eosinophilia of peripheral blood was seen on admission, but the number of eosinophils decreased after the octreotide therapy and normalised when pleural effusion disappeared. Octreotide is one of the effective options for the treatment of pancreatic pleural effusion.
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PMID:Marked effect of octreotide acetate in a case of pancreatic pleural effusion. 1119 Oct 6

Pancreatitis is rightly the most feared complication of endoscopic retrograde cholangiopancreatography (ERCP). Ten percent to 15% of cases of post-ERCP pancreatitis (PEP) are severe by clinical and radiologic criteria. Such cases carry significant morbidity and mortality and are responsible for the vast majority of ERCP-related deaths. The prediction and prevention of PEP have been of great interest to endoscopists since the introduction of ERCP 30 years ago. Prediction and diagnosis of PEP have become more accurate with the widespread availability of serum amylase estimation. A variety of cytokines (eg, interleukin -1, IL-6, and IL-8) and acute phase reactants (eg, C-reactive protein) are also elevated in the serum in acute pancreatitis, and these form the basis of evolving tests for PEP. Urine testing (for amylase) in acute pancreatitis is obsolete, but it may soon undergo a revival in the form of a rapid (3-minute) dipstick test for trypsinogen-2, a sensitive and specific test for this disease. The prevention of PEP takes multiple forms. The following steps are recommended for clinicians: 1) avoid ERCP when other, less invasive or noninvasive imaging tests can do the job (eg, CT or magnetic resonance imaging); 2) avoid high-risk (of PEP) procedures, such as needle-knife papillotomy, balloon dilation of the biliary sphincter, and pancreatic sphincterotomy, and take steps to reduce risk when these procedures are unavoidable; 3) ensure that those who perform ERCP have adequate training and experience; and 4) consider pharmacologic intervention. Despite a depressing catalog of drug interventions that have failed over the years (eg, antihistamines, anticholinergics, and corticosteroids), three agents have recently shown promise: somatostatin; its octapeptide analogue, octreotide; and gabexate mesylate, a protease inhibitor.
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PMID:Predicting and preventing post-ERCP pancreatitis. 1190 Jun 75

In massive hemorrhage from acute gastric mucosal lesions, it is occasionally difficult to control the bleeding with nonsurgical therapy. We used the somatostatin analog, octreotide, which suppresses gastric and pancreatic function, to treat severe hemorrhagic erosive gastritis in a patient with acute pancreatitis. A 22-year-old man presented with epigastralgia and melena. Blood levels of pancreatitis markers were elevated. Computed tomography revealed diffuse enlargement of the pancreas, without fluid collection around the organ. An endoscopic examination showed extensive hemorrhagic erosions over almost the whole gastric mucosa. We diagnosed extensive hemorrhagic erosive gastritis with acute pancreatitis. A protease inhibitor (nafamostat mesilate 50 mg/day) and an H(2) receptor antagonist (famotidine 40 mg/day) were administered by injection for 6 days; the patient's serum and urine amylase levels fell, but the gastric erosions with hemorrhage were not attenuated. Octreotide was given subcutaneously, at a daily dose of 100 microg for 5 days, without famotidine administration. His melena disappeared, and the gastric erosions were markedly decreased. Administration of the somatostatin analog, octreotide, proved to be effective treatment in a patient with severe hemorrhagic erosive gastritis associated with acute pancreatitis.
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PMID:Extensive hemorrhagic erosive gastritis associated with acute pancreatitis successfully treated with a somatostatin analog. 1237 48

The aim of the present review is to summarize the current knowledge regarding pharmacological prevention and treatment of acute pancreatitis (AP) based on experimental animal models and clinical trials. Somatostatin (SS) and octreotide inhibit the exocrine production of pancreatic enzymes and may be useful as prophylaxis against post endoscopic retrograde cholangiopancreatography pancreatitis (PEP). The protease inhibitor gabexate mesilate (GM) is used routinely as treatment to AP in some countries, but randomized clinical trials and a meta-analysis do not support this practice. Nitroglycerin (NGL) is a nitrogen oxide (NO) donor, which relaxes the sphincter of Oddi. Studies show conflicting results when applied prior to ERCP and a large multicenter randomized study is warranted. Steroids administered as prophylaxis against PEP has been validated without effect in several randomized trials. The non-steroidal anti-inflammatory drugs (NSAID) indomethacin and diclofenac have in randomized studies showed potential as prophylaxis against PEP. Interleukin 10 (IL-10) is a cytokine with anti-inflammatory properties but two trials testing IL-10 as prophylaxis to PEP have returned conflicting results. Antibodies against tumor necrosis factor-alpha (TNF-alpha) have a potential as rescue therapy but no clinical trials are currently being conducted. The antibiotics beta-lactams and quinolones reduce mortality when necrosis is present in pancreas and may also reduce incidence of infected necrosis. Evidence based pharmacological treatment of AP is limited and studies on the effect of potent anti-inflammatory drugs are warranted.
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PMID:Pharmacological approach to acute pancreatitis. 1885


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