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)

The latency to tail-flick response in the rat was significantly prolonged by cerebroventricular infusion of 1.0 microgram of somatostatin (SRIF) and more so with 10.0 microgram. The D-tryptophan analog was less effective than native SRIF. Pretreatment with naloxone eliminated analgesia but not seizures induced by SRIF. Recording of the EEG activity enabled determination of the specific state of the sleep-waking cycle in which the repeated tail-flick responses were tested: latency was generally longer in both control and test animals when tail immersion was performed during the state of sleep or drowsiness rather than during the awake state. Although animals receiving SRIF were less likely to fall asleep between subsequent test trails, the average latency was actually longer than after control saline infusion when the animals slept more. SRIF, unlike other releasing factors and peptides tested, showed significant activity in an opiate radioreceptor assay. The blockade of SRIF action by naloxone pretreatment, along with binding of SRIF to opiate receptors in vitro, suggest opiate receptors to be involved in the mediation of analgesia observed in present study.
 ...
PMID:Opiate-like naloxone-reversible actions of somatostatin given intracerebrally. 63 75

Six stereochemically pure analogues of somatostatin (SS), D- and L-5F-Trp8-SS, D- and L -6F-Trp8-SS, and D- and L-5Br-Trp8-SS, were synthesized and found to be more potent than somatostatin in suppressing the release of growth hormone from cultured rat pituitary cells. Two of the analogues, D-5F-Trp8- and D-5Br-Trp8-SS, were respectively 25 and 30 times more active than somatostatin in that assay. The analogues were prepared by solid phase synthesis of their corresponding diastereomeric mixtures, followed by their complete resolution by preparative partition chromatography. Reversed phase high pressure liquid chromatography (HPLC) was used to monitor the resolution and also to check the final purity of each peptide. Positive identification of each diastereoisomer was determined by amino acid analyses of their enzymatic digests, direct comparison with a known all-L standard in the case of the 5F-Trp8 analogues, and chromatographic separation of dansylated amino acids following enzymatic digestion of D- and L-5Br-Trp8-SS. The role of tryptophan in somatostatin is discussed and it is suggested that maintenance of physiological activity in somatostatin peptides, at least on the pituitary, is partially dependent upon the degree of resonance in the indole nucleus in position 8.
 ...
PMID:Highly active position eight analogues of somatostatin and separation of peptide diastereomers by partition chromatography. 67 12

Somatostatin 28 (S-28), originating in gastrointestinal cells, is secreted into the circulation and increases in humans after ingestion of a mixed meal. To evaluate the possibility that the increased levels of S-28 post cibum might modulate the release of enzymes and bicarbonate from the exocrine pancreas, S-28 was infused intravenously into healthy volunteers to levels seen after food intake. During S-28 infusion, the output of lipase, trypsin, amylase, and bicarbonate stimulated by either exogenous cholecystokinin octapeptide or endogenous signals from intraduodenal administration of tryptophan or a mixture of amino acids was significantly reduced. It is concluded that S-28 released from the gut during food intake modulates pancreatic exocrine function in humans.
 ...
PMID:Evidence for hormonal inhibition of exocrine pancreatic function by somatostatin 28 in humans. 135 58

This review integrates the clinical aspects of systemic sclerosis (SSc; scleroderma) and scleroderma-like conditions with new knowledge of the control of blood vessel tone and the role of anoxia in the activation of connective tissues leading to fibrosis. Serologic tests, high resolution computed tomographic scanning, bronchoalveolar lavage, and physiologic assessment of pulmonary gas diffusion are compared as diagnostic tools and as means of quantitating internal organ involvement. Treatment of Raynaud's disease and phenomenon, management of scleroderma renal crisis, and new means for improving gastrointestinal function with octreotide, the somatostatin analogue, also are discussed. The relationship between idiopathic forms of SSc and eosinophilic fasciitis/eosinophilia-myalgia syndrome caused by L-tryptophan ingestion and the scleroderma-like disease associated with silicone breast implants also is discussed.
 ...
PMID:The many faces of scleroderma. 135 85

Plasma somatotropin (ST) levels are depressed in the genetically obese Zucker rat compared to those of their littermates. It is believed that this defect is associated with one or both of the hypothalamic neuropeptides that control ST release: growth hormone releasing factor (GRF) and somatostatin (SS). The mechanism by which SS and GRF neuropeptides are regulated remains uncertain. The objective of this study was to examine the effect of 2 deoxy-glucose (2DG), isoproterenol (ISO), tryptophan (TRP), and 5HT on SS and GRF release in hypothalamic tissue from lean and obese Zucker rats. An in vitro perifusion system was established to examine the release of SS and GRF from perifused hypothalami taken from 8- and 12-week-old Zucker rats under basal conditions and in response to 2DG, ISO, TRP, 5HT, and KCl administration. Hypothalami were perifused with Dulbecco's modified eagle's medium continuously at 37 degrees C for 5 h at a flow rate of 100 ml/min. ISO and 2DG significantly (p < 0.05) increased SS levels from the obese rat, but no effect was observed from the lean littermate. GRF was not affected by 2DG or ISO in either genotypes. TRP and 5HT failed to affect SS or GRF release in lean or obese Zucker rats. It is proposed that the obese Zucker rat is more sensitive to glucose deprivation and to beta-adrenergic stimulation of SS release than the lean littermate.
 ...
PMID:Somatostatin and growth hormone-releasing factor release from Zucker rat hypothalamic tissue. 136 77

The electrochemical activity of catechol- and indoleamines, measured by differential pulse voltammetry (DPV) with specifically electrically pretreated carbon fiber microelectrodes, has been utilized to develop sensitive assays for amine neurotransmitters and metabolites. So far, four oxidation peaks have been recorded in vivo between -200 and +500 mV and are well identified. We now report that by increasing the potential sweep range to +950 mV, a further peak, called Peak 5, was detected at +800 mV in vivo in the striatum of anesthetized rats. Neuropeptides containing tyrosine, tryptophan and/or cysteine appear to be electrochemically active between +600 and +900 mV in vitro in a buffered solution at pH 7.4. The present study investigates the chemical nature of Peak 5 and the possible contribution of electroactive neuropeptides to this in vivo voltammetric signal. Experiments performed in vitro and in vivo with amino acids, neuropeptides, or bacitracin (a potent peptidase inhibitor) support the view that Peak 5 is peptidergic. Furthermore, peripheral administration of cysteamine and intrastriatal injection of specific somatostatin antisera both cause the eventual disappearance of Peak 5, suggesting that somatostatin (which oxidases in vitro at approx +800 mV), or a structurally related peptide, could be the principal component of striatal Peak 5.
 ...
PMID:In vivo voltammetric detection of neuropeptides with micro carbon fiber biosensors: possible selective detection of somatostatin. 167 55

Canine jejunal epithelial cells were isolated and maintained in short-term culture to study cholecystokinin (CCK) release. Sequential digestion of jejunal mucosa with collagenase and ethylenediaminetetraacetic acid was followed by counterflow elutriation to enrich CCK-containing cells. After 40 hours in culture on collagen-coated plates, 8.4% of the initially seeded cells were attached; 8.7% of them stained positive with a C-terminal CCK/gastrin antibody and 2.5% stained positive with a gastrin-specific antibody. Basal release of CCK into the culture medium amounted to 1.3% of total cell content over 105 minutes. Receptor-independent stimulation of protein kinase C by the phorbol ester beta-phorbol-12-myristate-13-acetate caused significant CCK release. The inactive form, 4 alpha-phorbol-12-myristate-13-acetate, had no effect. Activation of adenylate cyclase by 10(-5) mol/L forskolin evoked a 2.5-fold increase in CCK concentrations, which was completely abolished by 10(-8) mol/L somatostatin. L-phenylalanine stimulated CCK release at 20 and 50 mmol/L, whereas D-phenylalanine caused significant hormone output only at 50 mmol/L. L-tryptophan had no effect. Cholecystokinin release stimulated by L-phenylalanine was not influenced by the addition of either somatostatin or somatostatin antibody. In conclusion, a system of isolated canine jejunal epithelial cells was developed in short-term culture. This preparation proved suitable for the study of CCK release on a cellular basis.
 ...
PMID:Cholecystokinin release from isolated canine epithelial cells in short-term culture. 172 60

Somatostatin was degraded by the synaptic membrane from rat hippocampus. Cleavage products were separated by reversed phase high performance liquid chromatography and identified by amino acid composition analyses and N-terminal amino acid and sequence determinations around the cleavage sites. Fragments produced from the cleavages at both or either sites between the Phe6-Phe7 and/or between the Thr10-Phe11, together with free phenylalanine and tryptophan, were major cleavage products, followed by that produced from the cleavage of the Asn5-Phe6 bond. The accumulation of the major cleavage products, as well as the initial cleavage of somatostatin, was strongly inhibited by metal chelators and also by specific inhibitors of endopeptidase-24.11 (EC 3.4.24.11), phosphoramidon and thiorphan. The inhibitor susceptibility of the synaptic membrane toward somatostatin was similar to that toward Leu-enkephalin, a natural substrate of endopeptidase-24.11. Furthermore, endopeptidase-24.11 purified from rat brain hydrolyzed somatostatin at the cleavage sites identical to those by the hippocampal synaptic membrane. Thus, it can be concluded that endopeptidase-24.11 plays a major role in the initial stage of somatostatin degradation in rat hippocampus.
 ...
PMID:The degradation of somatostatin by synaptic membrane of rat hippocampus is initiated by endopeptidase-24.11. 197 74

We report the conformational analysis of a series of cyclic hexapeptides related to the hormone somatostatin utilizing 1H NMR spectroscopy and NOE restrained molecular dynamics. The conformational preferences and results from biological analysis of these analogs (previous paper) allow for refinement of the current understanding of the structure-activity relationship of somatostatin. For most of the molecules examined, a beta II' turn about the D-tryptophan-lysine residues, postulated to be required for biological activity, was present. From the NOE restrained molecular dynamics, it can be seen that the turn structure is important for the maintenance of the proper orientation of the side chains of the adjacent phenylalanine, tryptophan and lysine. The biologically active analogs have the side chains of lysine and D-tryptophan extended away from the 18-membered ring in close proximity to each other for a significant portion of the dynamic simulations. Although other conformations are accessible and monitored during the simulations, we believe this is important for biological recognition. The absence of the beta II' turn at the D-tryptophan-lysine disrupts this side chain array producing inactive molecules. The role of the bridging region, the Phe-Pro dipeptide, is to stabilize the beta II' turn and help maintain the proper orientation of the biologically important side chains.
 ...
PMID:Cyclic hexapeptides related to somatostatin. Conformational analysis employing 1H-NMR and molecular dynamics. 198 Apr 90

The cyclic peptide SMS 201-995 (+)D-Phe1-Cys2-Phe3-D-Trp4-(+)Lys5-Thr6-++ +Cys7-Thr(ol)8 is an analog of somatostatin and binds to lipid membranes by an electrostatic/hydrophobic mechanism. The structural changes accompanying the binding process were investigated with circular dichroism (CD), fluorescence spectroscopy, and phosphorus and deuterium nuclear magnetic resonance. The peptide penetrates into the lipid bilayer and the binding is accompanied by a small change in the CD spectrum suggesting the formation of beta-ordered structures. The fluorescence emission spectrum of the tryptophan side chain exhibits a blue shift and an intensity enhancement of the emission maximum, providing evidence that this residue is located in the inner part of the phospholipid headgroup region with a dielectric constant of epsilon approximately 7. The peptide diffuses rapidly in the plane of the membrane, changing the lipid headgroup conformation. This was demonstrated by selectively deuterating the two choline segments and measuring the deuterium spectra as a function of the bound peptide concentrations. A linear variation of the quadrupole splitting with the mol fraction of bound peptide was observed. The molecular origin of this effect is a distinct change in the orientation of the phosphocholine dipole, moving the N+ end of the dipole away from the membrane surface into the water phase. This type of headgroup rotation appears to be the general response of the zwitterionic phosphocholine headgroup to cationic surface charges. However, peptides appear to be the most efficient modulators of the lipid headgroup structure known to date.
 ...
PMID:Peptide binding to lipid membranes. Spectroscopic studies on the insertion of a cyclic somatostatin analog into phospholipid bilayers. 199 58


1 2 3 4 5 6 Next >>