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

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.
NIDA Res Monogr 1986
PMID:A membrane bound substance P degrading endopeptidase from rat brain. 244 28

H-D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP) exhibited high affinity (IC50 = 2.80 nM) in displacing [3H]naloxone binding (nH = 0.89 +/- 0.1) and showed an exceptional selectivity for mu opioid receptors with an IC50(DPDPE)/IC50(naloxone) ratio of 4,840, while it displayed very low affinity for somatostatin receptors (IC50 = 22,700 nM) in rat brain binding assays. [3H]CTOP was recently custom synthesized (spec. act.: 84 Ci/mmol) and evaluated for its in vitro binding properties towards the mu opioid receptors in rat brain membrane preparations. Association and dissociation of [3H]CTOP binding to mu opioid receptors were rapid at 25 degrees C with a kinetic Kd value of 0.67 nM. Saturation experiments gave apparent Kd value of 1.11 nM and Bmax value of 136 +/- 13 fmol/mg prot at 25 degrees C. Specific [3H]CTOP binding was inhibited by a number of different opioid and opiate ligands. Among them, putative mu opioid receptor-specific ligands, such as naloxone, naltrexone and CTOP inhibited the binding with high affinity, while delta opioid receptor-specific compounds or non-opioid drugs inhibited specific [3H]CTOP binding with low affinity or they were ineffective.
NIDA Res Monogr 1986
PMID:H-D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2: a potent and selective antagonist opioid receptors. 289 64

A 72-year-old man with Crohn's disease for about 6 years was urgently hospitalized in hypovolaemic shock. On admission, serum creatinine concentration was 4.2 mg/dl, serum sodium 124 mmol/l, as a result of massive fluid and electrolyte loss via a loop ileostomy which had been placed 4 weeks previously because of a complicated perianal fistula. The basic aetiology of the diarrhoea probably lay in the previous resection of 30 cm of terminal ileum, other possible causes having been excluded. The ileostomy diarrhoea persisted despite the administration of loperamide, ranitidine, glucocorticoids, opium and pancreatic enzymes. Metronidazole, given in case the diarrhoea was due to a change in bacterial flora, also failed to achieve improvement. But when the somatostatin analogue octreotide was administered, the fluid loss via the ileostomy was quickly reduced so that both fluid and electrolyte infusions could be stopped. In subsequent months the initially required daily octreotide dosage of three times 100 micrograms could be reduced to once 50 micrograms subcutaneously. But it was not possible to stop this drug completely: it has now been continued and well tolerated for 2 years.
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PMID:[Successful treatment of a life-threatening ileostomy diarrhea with the somatostatin analog octreotide]. 800 65

We investigated the mechanisms by which peripheral or portal insulin can independently alter liver glucose production. Isotopic ([3-3H]glucose) and arteriovenous difference methods were used in conscious overnight-fasted dogs. A pancreatic clamp (somatostatin plus basal insulin and basal glucagon infusions) was used to control the endocrine pancreas. After a 40-min basal period, a 180-min experimental period followed in which selective increases in peripheral (PERI group, n = 5) or portal-vein (PORT group, n = 5) insulin were induced. In control dogs (CONT group, n = 10), insulin was not increased. Glucagon levels were fixed in all studies, and basal euglycemia was maintained by peripheral glucose infusion in the two experimental groups. In the PERI group, arterial insulin rose from 36 +/- 12 to 120 +/- 12 pmol/l, while portal insulin was unaltered. In the PORT group, portal insulin rose from 108 +/- 42 to 192 +/- 42 pmol/l, while arterial insulin was unaltered. Neither arterial nor portal insulin changed from basal in the CONT group. With a selective rise in peripheral insulin, the net hepatic glucose output (NHGO; basal, 11.8 +/- 0.7 micromol x kg-1 x min-1) did not change initially (11.8 +/- 2.1 micromol x kg-1 x min-1, 30 min after the insulin increase), but eventually fell (P < 0.05 ) to 6.1 +/- 0.9 micromol x kg-1 x min-1 (last 30 min). With a selective rise in portal insulin, NHGO dropped quickly (P < 0.05) from 10.0 +/- 0.9 to 5.6 +/- 0.6 micromol x kg-1 x min-1 (30 min after the insulin increase) and eventually reached 3.1 +/- 1.1 micromol x kg-1 x min-1 (last 30 min). When insulin levels were not increased (CONT group), NHGO dropped progressively from 10.1 +/- 0.6 to 8.3 +/- 0.6 micromol x kg-1 x min-1 (last 30 min). Conclusions drawn from the net hepatic glucose balance data were confirmed by the tracer data. Net hepatic gluconeogenic substrate uptake (three carbon precursors) fell 2.0 micromol x kg-1 x min-1 in the PERI group, but rose 1.2 micromol x kg-1 x min-1 in the PORT group and 1.2 micromol x kg-1 x min-1 in the CONT group. A selective 84 pmol/l rise in arterial insulin was thus associated with a fall in NHGO of approximately 50%, which took 1 h to manifest. Conversely, a selective 84 pmol/l rise in portal insulin was associated with a 50% fall in NHGO, which occurred quickly (15 min). From the control data, it is evident that in either case approximately 30% of the fall in NHGO was due to a drift down in baseline and that 70% was due to the rise in insulin. In conclusion, an increment in portal insulin had a rapid inhibitory effect on NHGO, caused by the suppression of glycogenolysis, while an equal increment in arterial insulin produced an equally potent but slower effect that resulted from a small increase in hepatic sinusoidal insulin, from a suppression of gluconeogenic precursor uptake by the liver, and from a redirection of glycogenolytic carbon to lactate rather than glucose.
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PMID:A comparison of the effects of selective increases in peripheral or portal insulin on hepatic glucose production in the conscious dog. 886 66

The liver is a parenchymal organ that has a substantial capacity to regenerate after damage. Obstructive jaundice is a common surgical disease and potentially risky. A successful outcome of operations depends upon the hepatic regeneration reserve. Insulin is one of factors responsible for hepatotrophic regeneration and somatostatin has a reversal suppressive action. Experimental obstructive jaundice was introduced and relieved. In addition, serum insulin and somatostatin concentrations were measured. We used immuno-histochemical study of pancreatic tissue by immunogold to express the tissue relative insulin and somatostatin concentrations. Nucleolar organizer regions (NORs) were used to predict the nucleolar activity of liver cells. In our studies, we observed the serum concentrations of insulin and somatostatin were similar to the relative tissue concentration in pancreatic tissues. The relative tissue gold-particle score of insulin in group A (rats with common bile duct tied), was CONT: T4: T7: T14 = 100%: 90.5%: 68.3%: 46.2%; of somatostatin was 100%: 120%: 118.2%: 115.5% respectively. In group B (common bile duct tied for 4 days then relieved), the gold-particle score of insulin was T4: T4R4: T4R7: T4R14 = 90.5%: 62.8%: 72.2%: 95.4%; of somatostatin was 120.2%: 114.3%: 108.1%: 106.2% respectively. In group C (common bile duct tied for 7 days then relieved), the gold-particle score of insulin was T7: T7R4: T7R7: T7R14 = 68.3%: 53.3%: 73.5%; of somatostain was 118.2%: 109.4%: 104.6%: 102.1% respectively. The mean numbers of AgNORs in group A revealed CONT: T4: T7: T14 = 2.24 +/- 0.24: 3.02 +/- 0.96: 3.26 +/- 1.02:3.08 +/- 0.84, group B was T4: T4R4: T4R7: T4R14 = 3.02 +/- 0.96: 3.03 +/- 0.73: 3.36 +/- 1.12: 3.72 +/- 1.46, and group C showed T7: T7R4:T7R7: T7R14 = 3.26 +/- 1.02: 3.26 +/- 0.84: 3.31 +/- 1.24: 3.54 +/- 1.24. In conclusion, our studies suggested: (1) liver regeneration appeared promptly after obstructive jaundice developed, but prolonged cholestasis inhibited this process. (2) Insulin levels gradually fell during the process of obstructive jaundice. Those levels elevated when cholestasis was improved. Nevertheless, both insulin and hepatic regeneration power could not reflect the initial improvement of cholestasis simultaneously. It took a longer time for the improvement of cholestasis and the recovery of the liver function. (3) Patho-physiologically, somatostatin had a weak influence on hepatic regeneration during obstructive jaundice. (4) Our studies provided clues that early biliary drainage might improve hepatic regeneration capacity. Supplement of insulin during the obstructive jaundice might be helpful for the improvement of hepatic regeneration power.
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PMID:Changes of insulin and somatostatin and their relationship to liver regeneration in experimental obstructive jaundice. 942 63

Quadruple therapy (with a proton pump inhibitor (PPI), metronidazole, tetracycline and bismuth) is generally reserved for second-line treatment; however, studies using this regimen for 7 days have found it to be effective even in metronidazole-resistant strains. Resistance is an ongoing problem with antimicrobial therapy but considerable progress has now been made into understanding the underlying genetic mechanisms of this process. Metronidazole resistance in Europe is usually in the range of 20-30% of strains but may be as high as 70% in some countries. One genetic mechanism involved is thought to be a mutation of the rdxA gene. Macrolide resistance appears to be on the increase in Europe, varying from 1% in some countries to 13% in others. The genetic mechanism involved has been shown to be a point mutation of a ribosomal RNA. Amoxicillin resistance is an emerging problem that has an adverse effect on eradication rates in clinical practice. Resistance has been shown to be caused by the absence of one of the four binding proteins in the cell wall. Few novel antibiotics have been developed for use in eradication therapy, although rifabutin, secnidazole and furazolidone have shown some success as part of combination therapy. Alternative therapies that have been tested include mucosal protective agents which have been used in place of a PPI in some eradication regimens with some success, and the somatostatin analog, octreotide, that has been used as part of quadruple therapy in place of a PPI and produced eradication rates of approximately 88%. The ultimate challenge is still to develop a safe and effective vaccine against Helicobacter pylori. Current and future research will also focus on identifying genetic targets for therapy, adhesion molecule analogs to prevent binding of the bacterium, and urease inhibitors. The current triple therapy treatment options available for the eradication of Helicobacter pylori infection are over 90% effective in susceptible organisms and there are very few medical conditions to which we can offer such efficacious treatment. Unfortunately, the recommendations made at consensus conferences are not always put into practice and physicians in primary care may be unaware of the true efficacy of eradication therapy. Treatment is very simple: three drugs, twice a day for 1 week. The main focus for both primary care physicians and gastroenterologists should be to reinforce the need for patient compliance, otherwise we will see an increase in antibiotic resistance. Patients should be prewarned that they may experience some mild side effects and should be encouraged to complete the course of treatment. The real challenge for the future will be the management of patients who do not respond to first-line treatment. This paper will focus on potential problems with therapy, such as antibiotic resistance, and possible future solutions, such as novel antibiotics and vaccines.
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PMID:Challenges to therapy in the future. 1082 51