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)

The opioid receptor antagonist properties of four conformationally constrained cyclic octapeptide analogues of somatostatin were investigated using in vitro functional paradigms of mu-, delta- and kappa-opioid receptors in the rat brain. The analogues examined were D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2 (CTOP), D-Phe-Cys-Tyr-D-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP), D-Tic-CTOP (TCTOP) and D-Tic-CTAP (TCTAP). Activation of mu-receptors by the enkephalin analogue Tyr-D-Ala-Gly-(NMe)Phe-Gly-ol (DAGO) inhibited the (electrically evoked) release of [3H]noradrenaline (NA) from superfused cortical slices and this inhibitory effect was antagonized in a competitive fashion by all of the octapeptides tested (pA2 values: CTOP and CTAP 7.9-8.0, TCTOP and TCTAP 8.7-8.8). Selective activation of kappa-opioid receptors by the cyclohexylbenzeneaceamide U69593 (0.02 microM) inhibited (by 40-45%) the release of [3H]dopamine (DA) from striatal slices, whereas selective activation of delta-opioid receptors by [D-Ser2(O-t-butyl),Leu5]enkephalyl-Thr6 (DSTBULET; 0.1 microM) caused an inhibition (by 38-46%) of striatal [14C]acetylcholine (ACh) release. However, these inhibitory effects were not affected by any of the octapeptides in concentrations that caused full antagonism of the inhibitory effect (55-65%) of 0.1 microM DAGO on cortical [3H]NA release. Thus, the cyclic octapeptide somatostatin analogues CTOP, CTAP, TCTOP and TCTAP are potent and highly selective antagonists at the mu-opioid receptors mediating presynaptic inhibition of NA release in the brain. The mu-receptor affinity of the most potent of these antagonists, TCTOP and TCTAP, appears to be similar to that of naloxone but these antagonists have a much greater selectivity than the latter.
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PMID:Cyclic somatostatin analogues as potent antagonists at mu-, but not delta- and kappa-opioid receptors mediating presynaptic inhibition of neurotransmitter release in the brain. 168 63

The localization and distribution of seven neuropeptides in the nervous system of the plerocercoid, adult and free proglottis stages of the tetraphyllidean tapeworm Trilocularia acanthiaevulgaris have been determined by an indirect immunofluorescence technique. Six of the peptides are vertebrate-derived, namely, pancreatic polypeptide (PP), peptide tyrosine tyrosine (PYY), vasoactive intestinal polypeptide (VIP), peptide histidine isoleucine (PHI), substance P (SP) and somatostatin (SRIF); the seventh is the invertebrate neuropeptide, FMR Famide. This is the first demonstration of VIP and SP immunoreactivity in a cestode parasite, and for SRIF this is its first description in any parasitic platyhelminth. Cell bodies and nerve fibres immunoreactive to PP, PYY, VIP, SP and FMRFamide are present throughout the CNS; the distributions of PHI and SRIF were more restricted. In the PNS, nerve fibres immunoreactive to PP occur in the bothridia, whilst in the free proglottis nerve fibres immunoreactive to PYY and VIP innervate the gonads; VIP-immunoreactive nerve elements also supply the reproductive ducts. Extra-neuronal sitings of peptide immunoreactivities were evident for PHI, in association with the excretory system, and for SRIF, in presumed tegumental cell bodies in the free proglottis. The results are discussed in relation to the possible roles of the peptides in the neurophysiology and developmental biology of the worm.
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PMID:Peptidergic nerve elements in three developmental stages of the tetraphyllidean tapeworm Trilocularia acanthiaevulgaris. An immunocytochemical study. 169 77

Light microscopic immunocytochemistry was utilized to localize populations of neurons in the human retina immunoreactive for the following neuroactive peptides: substance P (SP), vasoactive intestinal polypeptide (VIP), somatostatin (SOM) and LANT-6-(H-Lys-Asn-Pro-Tyr-Ile-Leu-OH), a hexapeptide which is identical to the C-terminal half of neurotensin except for the amino acid substitutions Lys/Arg and Asn/Arg. The majority of SP immunoreactive cells were amacrine cells whose pear-shaped or oval cell bodies (about 8 microns in diameter) were situated in the proximal parts of the inner nuclear layer. A small number of SP-stained somas (about 10-15 microns in diameter) were located in the ganglion cell layer and were designated as those of displaced amacrine cells. The SP-immunoreactive processes were distributed in sublamina 1, 3 and 5 with the most dense plexus being found in sublamina 3 of the inner layer. VIP-positive cell bodies (8-9 microns) were oval or pear-shaped and were situated in the innermost cell rows of inner nuclear layer. The majority of fine VIP-immunoreactive processes extended to sublamina 3 with only a few branches distributing in sublamina 1 of the inner plexiform layer. The SOM-stained cell bodies (10-11 microns) were round and were situated in the innermost cell rows of inner nuclear layer. SOM-positive processes were observed in sublamina 1 and 2 of the inner plexiform layer. The LANT-6 immunoreactive cell bodies (12-22 microns) were either oval-, round- or pyriform-shaped and were situated in ganglion cell layer.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Localization of neuropeptide-immunoreactive neurons in the human retina. 169 34

Somatostatin-14 (SS-14) and somatostatin-28 (SS-28) produce concentration dependent reductions in short-circuit current in rat colonic mucosa. EC50 values of 15.0 and 13.3 nM were obtained for SS-14 and SS-28 respectively while the N-terminal fragments of SS-28, namely somatostatin-(1-12) (SS1-12) and somatostatin-(1-14) (SS1-14) were inactive. Cyclo(Pro-Phe-D-Trp-Lys-Thr-Phe) and cyclo(Pro-Tyr-D-Trp-Lys-Thr-Phe) were potent antisecretory peptides, like SS-14 and SS-28; while the putative somatostatin antagonist, cyclo(7-aminoheptanoyl-Phe-D-Trp-Lys-Thr[Bzl]) exhibited neither agonist nor antagonist effects. Responses to SS-14 could be regulated by agents which affected the secretory state of the epithelium. Antisecretory effects of SS-14 were markedly attenuated by piroxicam and were restored following piroxicam plus either forskolin or vasoactive intestinal polypeptide (VIP). SS-14 also attenuated secretory responses produced by carbachol, substance P (SP), VIP and alpha- and beta-calcitonin gene related peptide (alpha-, beta-CGRP). Therefore, SS-14 exhibits broad spectrum antisecretory effects in rat descending colon mucosa.
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PMID:The antisecretory effects of somatostatin and analogues in rat descending colon mucosa. 170 67

An endopeptidase was isolated from Xenopus laevis skin secretions. This enzyme, which has an apparent molecular mass of 100 kDa, performs a selective cleavage at the Xaa-Phe, Xaa-Leu, or Xaa-Ile bond (Xaa = Ser, Phe, Tyr, His, or Gly) of a number of peptide hormones, including atrial natriuretic factor, substance P, angiotensin II, bradykinin, somatostatin, neuromedins B and C, and litorin. The peptidase exhibited optimal activity at pH 7.5 and a Km in the micromolar range. No cleavage was produced in vasopressin, ocytocin, minigastrin I, and [Leu5]enkephalin, which include in their sequence an Xaa-Phe, Xaa-Leu, or Xaa-Ile motif. The endopeptidase activity was inhibited by divalent cation chelators and by phosphoramidon only at high concentrations (IC50 = 50 microM), whereas it was insensitive to classical inhibitors of chymotrypsin, angiotensin convertase, and serine and cysteine peptidases, as well as carboxypeptidases. It is hypothesized that this enzyme, which is distinct from neutral endopeptidase (EC 3.4.24.11), constitutes the prototype of a family of related metalloendopeptidases that inactivate peptide substrates by cleavage at the Xaa-Phe, Xaa-Leu, or Xaa-Ile bond.
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PMID:A peptide-hormone-inactivating endopeptidase in Xenopus laevis skin secretion. 172 23

A modern method is reported for the assignment of absolute configuration for peptidomimetics in bioactive peptides by use of 1H-NMR parameters in solution. Four peptide systems incorporating either retro-inverso modifications or 2-aminocyclopentanecarboxylic acid (2-Ac5c) as a peptidomimetic for proline are discussed. (1) Two 14-membered cyclic dermorphin analogs Tyr-c[D-A2bu-Phe-gPhe-(S and R)-mLeu] with a reverse amide bond between gPhe and mLeu residues where gPhe denotes a gem-diamino analog of Phe and mLeu refers to a malonyl analog of Leu. (2) Two cyclic hexapeptides related to somatostatin, c[gSar6-(S and R)-mPhe7-D-Trp8-Lys9-Thr10-Phe11], with a reverse amide bond between the gSar and mPhe residues where the gSar and mPhe denote the gemdiamino and malonyl analogs of the Sar and Phe residues, respectively. The superscript numbers refer to positions in native somatostatin. (3) Cyclic hexapeptide somatostatin analogs containing 2-Ac5c [trans-(1S,2S)-2-Ac5c, trans-(1R,2R)-2-Ac5c,cis-(1R,2S)-2-Ac5c, and cis-(1S,2R)-2-Ac5c] in place of proline c[(2-Ac5c)6-Phe7-D-Trp8-Lys9-Thr10-Phe11]. (4) Morphiceptin related analogs incorporating a cis-2-Ac5c residue as shown in Tyr-cis-2-Ac5c-Phe-Val-NH2. The methodology described in this investigation could be applied to a wide variety of peptide systems.
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PMID:Absolute configuration for peptidomimetic residues in bioactive peptides. 174 64

Hormonal changes and whole blood free amino acid levels and their relation to renal function were measured in 12 insulin-dependent diabetic patients after two 10-day periods with a diet consisting of 10% and 20% respectively of the energy as protein. The patients were 15-21 years old and mean duration of diabetes was 12 (5-20) years. Glomerular filtration rate, renal plasma flow, and albumin excretion rate were measured together with plasma concentrations of glucagon, growth hormone, insulin-like growth factor 1 (IGF-1), somatostatin, serum insulin and free amino acids in blood. Glomerular filtration rate was 123 +/- 3 ml/min/1.73 m2 on high protein diet and 113 +/- 3 ml/min/1.73 m2 on low protein diet (p = 0.02). Renal plasma flow was unchanged. Glucagon, IGF-1, branch chained amino acids (BCAA), tyrosine, phenylalanine, lysine, and methionine were increased after the high protein diet. Growth hormone, somatostatin, insulin, and other amino acids remained unchanged. The increase in glomerular filtration rate was significantly correlated to the increase in glucagon, isoleucine, and valine (glucagon r = 0.71, p = 0.01, isoleucine r = 0.59, p = 0.04, valine r = 0.62, p = 0.03). In a multiple regression model the increase in glomerular filtration correlated most strongly to the increase in isoleucine, followed by valine and glucagon. Together these variables explained 88% of the total variance of the change in glomerular filtration rate (r2 = 0.88, p = 0.001). Albumin excretion rate was correlated to IGF-1 (r = 0.86, p less than 0.001) on the high protein diet.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Indications that branched chain amino acids, in addition to glucagon, affect the glomerular filtration rate after a high protein diet in insulin-dependent diabetes. 180 76

The effects of glucagon deficiency and excess on plasma leucine, lysine, and alanine were examined in six healthy young adult men, with primed continuous infusions of L-[1-13C]- or L-[5,5,5-2H3]leucine, L-[alpha-15N]-lysine, and L-[3-13C]alanine for 150 min before and during 210 min of either a glucagon-deficient euglycemic state (experiment 1), a basal glucagon state (experiment 2), or a glucagon-excess state (experiment 3). Steady-state plasma hormone levels were achieved by infusion of somatostatin (250 micrograms/h) and insulin (0.07 mU.kg-1.min-1), without (experiment 1) or with an infusion of glucagon at 0.7 ng.kg-1.min-1 (experiment 2) or 2.5 ng.kg-1.min-1 (experiment 3). Plasma branched-chain amino acid (AA) concentrations did not change with altered glucagon status, whereas significant differences were observed for plasma lysine, alanine, glycine, serine, threonine, proline, tyrosine, citrulline, and ornithine levels (0.05 greater than P greater than 0.001). Plasma leucine, lysine, and alanine fluxes and the rate of de novo alanine synthesis showed no significant changes with either glucagon deficiency or excess. These findings lead to the conclusion that glucagon-induced alterations in plasma AA profiles are not due to changes in the rate of appearance of AA from peripheral tissues but rather a consequence of changes in the fate of AA within the splanchnic region.
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PMID:Plasma amino acid kinetics during acute states of glucagon deficiency and excess in healthy adults. 196 9

The binding characteristics of several somatostatin (SS-14) analogs developed in our laboratory were examined in various human and animal tumors and normal tissues. In rat cerebral cortex and human breast cancer membranes the interaction of SS-14 with its binding sites was rapid, specific, saturable, linear with protein concentrations, and dependent on time and temperature. Analysis of kinetic and equilibrium experimental data showed that the interaction of [125I-Tyr11]SS-14 with the binding sites in all normal and tumoral tissue specimens was consistent with the presence of a single class of noncooperative binding sites. Superactive octapeptide analogs of somatostatin-containing hexapeptide sequences Cys-Phe-D-Trp-Lys-Thr-Cys or Cys-Tyr-D-Trp-Lys-Val-Cys showed significant binding affinities to SS-14 receptors. Among these analogs, D-Trp-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NH2 (RC-98-I) showed the highest binding affinity to normal human pancreatic tissue and human pancreatic adenocarcinoma. In contrast, Sandostatin (SMS 201-995) bound only to normal pancreas, not to human pancreatic cancers. Analog RC-98-I also showed a high binding to human and rat prostate cancers. In human epithelial ovarian cancers and an arrhenoblastoma, analogs D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Trp-NH2 (RC-95-I), D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 (RC-121) and D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2 (RC-160) appeared to be the most potent in displacing labeled SS-14. Analogs Ac-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NH2 (RC-101-I) as well as RC-121, RC-160, and RC-95-I, but not SMS-201-995, showed high binding affinity in human breast cancers. In specimens of human meningioma the highest binding was found with analogs RC-121, RC-95-I, and RC-101-I. Since marked variations in binding affinities were noted for several analogs in the tissues of origin and the tumors, this suggest that differences may exist between somatostatin receptors not only in normal vs. cancerous tissues, but also among various tumors. Our findings also imply that some analogs could be therapeutically superior to others in the treatment of certain tumors.
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PMID:Evaluation of receptors for somatostatin in various tumors using different analogs. 196 67

This study was undertaken to determine the origin and forms of immunoreactive somatostatin (SLI) present in the pancreatic juice of cannulated nonanesthetized rats. The systemic origin of somatostatin (SS) was assessed from bolus intravenous injections of either I125-Tyr1-SS-14 or synthetic SS-14 under basal and stimulated pancreatic juice secretion, and from measurements of radioactivity and SS-14 in the collected juice. Gel filtration of pooled juice samples indicated that there were no forms of SS corresponding to standards of I125-Tyr1-SS-14 or SS-14, but radioactive material eluted in the area of either I125-Tyr or free iodine. Investigation of the presence of SS-14 in the juice by radioimmunoassay (RIA) led to the identification of a 23-kDa SS-like immunoreactive protein that did not correspond to any of the three known forms of SS present in the pancreatic tissue (Pro-SS, SS-28, and SS-14). By boiling the juice before the RIA, this 23-kDa protein was no longer detectable by RIA. These data suggest that this protein may be a "putative" enzyme, degrading the SS tracer in the RIA. This possibility is supported by the observation that boiled juice lost this capacity of interfering with the RIA. In conclusion, SS in the pancreatic juice, if present, is not from systemic origin and the juice contains an active thermosensitive substance degrading the SS tracer in the RIA.
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PMID:Origin and characterization of immunoreactive somatostatin in rat pure pancreatic juice. 196 58


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