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 cyclic analogue of somatostatin (SRIF), D-Phe-Cys-Tyr-D-Trp-Lys-Thr-Cys-Thr-NH2 (CTC), exhibits good affinity for both opioid and SRIF receptor systems. Its conformational properties were examined in water by high-field proton n.m.r. spectroscopy and compared with results previously obtained with structurally related analogues SMS 201-995 and Sandoz 204-090 in the same solvent. The assignments were made using 2 D-n.m.r. methods, especially long-range connectivities between neighbouring alpha protons, and between beta and aromatic protons. The 3JNH-C alpha H and delta delta/delta T values are compatible with an equilibrium between two gamma turns involving residues 2, 3 and 4 and residues 3, 4, and 5, respectively.
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PMID:Conformational study of a somatostatin analogue by high-field n.m.r. spectroscopy, in aqueous solution. 289 8

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.
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PMID:H-D-Phe-Cys-Tyr-D-Trp-Orn-Thr-Pen-Thr-NH2: a potent and selective antagonist opioid receptors. 289 64

The effect of somatostatin-14 (SST) and somatostatin analog D-Phe-Cys-Phe-D-Trp-Lys-Thr-Cys-Thr-NH2 (RC-102) on migration inhibition of human leukocytes induced by cardiac antigen or phytohemagglutinin (PHA) was investigated. Both SST and RC-102 augmented the migration inhibition, thus indicating the enhanced formation or action of the leukocyte migration inhibiting factor (LMIF). This finding provides additional evidence for the immunomodulatory action of somatostatin.
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PMID:Somatostatin and its analog enhance the formation of human leukocyte migration inhibiting factor: further evidence for immunomodulatory action of somatostatin. 289 63

The cyclostomes represent the first class of vertebrate in evolution to develop an endocrine pancreas. Two peptides with somatostatin-like immunoreactivity were isolated from the islet organ of one such cyclostome, the Atlantic hagfish (Myxine glutinosa). The primary structure of the more abundant peptide was established as: Ala-Val-Glu-Arg-Pro5-Arg-Gln-Asp-Gly-Gln10-Val-His-Glu-Pro- Pro15-Gly-Arg-Glu-Arg-Lys20-Ala-Gly-Cys-Lys-Asn25-Phe- Phe-Trp-Lys-Thr30-Phe-Thr-Ser-Cys. The second peptide, comprising 27% of the total immunoreactivity in the islet extract, was identical to mammalian somatostatin-14. The pathway of posttranslational processing of prosomatostatin in the hagfish islet differs markedly from the pathway in the higher vertebrates. In the mammalian pancreas, prosomatostatin is cleaved at the site of the single arginyl residue (corresponding to position 6 in hagfish somatostatin-34) and at the arginine-lysine site (corresponding to positions 19 and 20 in the hagfish peptide) to generate somatostatin-14 and somatostatin-28(1-12)-peptide. In the hagfish islet, Arg6 is not used as a cleavage site and cleavage at Arg19-Lys20 represents only a minor pathway of processing. The data provide further evidence of the strong evolutionary pressure to conserve the complete amino acid sequence of somatostatin-14.
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PMID:Primary structures of somatostatins from the islet organ of the hagfish suggest an anomalous pathway of posttranslational processing of prosomatostatin-1. 289 18

Three cyclic disulfide analogs related to somatostatin, D-Phe(1)-cyclo(Cys(2)-Tyr(3)-D-Trp(4)-Lys(5)-Thr(6)-Xxx(7))-Thr(8)- NH2 (where Xxx = L-Pen 1; L-Cys 3; or D-Pen 4) were examined in DMSO-d6 by one- and two-dimensional proton n.m.r. spectroscopy in order to analyze the conformational influence of the position-7 residue on the 20-membered disulfide ring. From these studies it was concluded that all three analogs maintain a beta II' turn solution conformation for the core tetrapeptide -Tyr(3)-D-Trp(4)-Lys(5)-Thr(6)-. However, the disulfide conformation differs in the analogs, with 1 and 3 having a left-handed and 4 a right-handed disulfide chirality.
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PMID:Proton n.m.r. investigation of conformational influence of penicillamine residues on the disulfide ring system of opioid receptor selective somatostatin derivatives. 289 39

The aim of this study was to evaluate the contribution of gluconeogenesis from amino acids in the development of fasting and absorptive hyperammonemia in cirrhosis. Somatostatin (SRIF), which is known to inhibit the hepatic disposal of gluconeogenic amino acids, was administered in a continuous infusion (500 micrograms/h) for 90 min before and 5 h after a protein meal (240 g of meat) in 11 overnight fasting patients. Plasma glucagon, insulin, gluconeogenic amino acids (GAA: alanine, serine, glycine, and threonine) and ammonia (NH3) were evaluated before the infusion, immediately before, and at 1, 3, and 5 h after the meal. As control study, the same protocol was randomly repeated in a different day with saline infusion. During the latter, a direct correlation was found between fasting glucagon and ammonia (r = 0.68; p less than 0.05). Fasting glucagon, insulin, and NH3 did not change, whereas alanine (p less than 0.05) and the GAA sum decreased (p less than 0.01). When SRIF was infused, fasting glucagon (p less than 0.05), insulin (p less than 0.05), and NH3 (p less than 0.05) decreased. Alanine did not change, and GAA sum increased (p less than 0.02). No correlations were found by plotting changes in glucagon or GAA sum and NH3. After the meal, SRIF infusion abolished the plasma response of glucagon and markedly reduced that of insulin, so that their area under the curve (AUC0-5) were reduced (p less than 0.005, for both), with respect to control study. Moreover, the AUC0-5 of alanine (p less than 0.005) and GAA sum (p less than 0.005) were increased, suggesting a reduced disposal of these compounds. In spite of this, the meal-induced early increase and the AUC0-5 of plasma NH3 observed during SRIF and saline infusion did not differ. Our results do not confirm the importance of gluconeogenesis from alpha-amino-nitrogens in determining the fasting ammonemia of cirrhosis, and suggest that this metabolic pathway does not significantly influence the protein meal-induced exacerbation of plasma ammonia.
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PMID:Role of gluconeogenesis from amino acids in determining fasting and absorptive levels of plasma ammonia in cirrhosis. 289 85

An endocrinologically-potent octapeptide analogue of somatostatin (SRIF), 3-(2-naphthyl)-D-Ala-Cys-Tyr-D-Trp-Lys-Val-Cys-Thr-NH2 (BIM-23014 C), was examined for its ability to inhibit the in vitro and in vivo growth of the human small cell lung carcinoma (SCLC) line, NCI-H69. When cultured cells were implanted into athymic nude mice, treatment (500 micrograms/injection, twice daily) resulted in a prolongation of lag time for the appearance of measurable tumors, and there was a marked inhibition of the growth rate. Indeed, peptide injection in the region of the tumor resulted in a complete regression of the NCI-H69 tumors. Withdrawal of BIM-23014 C treatment resulted in an acceleration of tumor growth indicating an antiproliferative rather the oncolytic action. A similar inhibition of tumor growth was also observed when solid tumors obtained from the first implantation were used as the donor tissues. In cell culture, the proliferation in the presence of a low concentration (10nM) of BIM-23104 C was also significantly retarded suggesting a direct mechanism of action.
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PMID:In vitro and in vivo inhibition of human small cell lung carcinoma (NCI-H69) growth by a somatostatin analogue. 289 54

1. Electrically evoked contractions of the rat anococcygeus muscle were inhibited in a concentration-dependent manner by somatostatin-14 (SS14), -28 (SS28) and two synthetic hexapeptide analogues: L-363,301 (Pro-Phe-D-Trp-Lys-Thr-Phe) and L-363,586 (N-Me-Ala-Tyr-D-Trp-Lys-Val-Phe), with pIC50 values of 7.41, 7.38, 7.07 and 8.34, respectively. 2. The inhibitory effects of SS14 were dependent on stimulation frequency and external calcium ion concentration. Calcium behaved as a non-competitive antagonist of SS14, it reduced the maximal inhibitory effect of the peptide and at a concentration of 5.08 mM it significantly affected the pIC50 value. 3. SS14 (3 x 10(-7) M) did not affect the tonic actions of bath-applied noradrenaline in the absence of field stimulation. 4. The effects of SS14 persisted in naloxone (10(-5) M) and were, therefore, not due to an action at opiate receptors. Furthermore, experiments involving the lyophilization of bath contents, showed no evidence to support an indirect mechanism involving the release of an endogenous inhibitory substance. 5. High concentrations (10(-5) M) of SS14 or L-363,301 inhibited the relaxation response evoked by electrical stimulation of guanethidine (3 x 10(-4) M)-treated preparations. 6. These results are consistent with similar actions of SS14 on other smooth muscle preparations and are presumed to reflect a presynaptic inhibition of transmitter release by a direct action on somatostatin receptors. The antagonistic effect of calcium on this response is discussed with reference to a possible role in receptor desensitization.
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PMID:The inhibitory effect of somatostatin peptides on the rat anococcygeus muscle in vitro. 290 39

Somatostatin may inhibit gastric exocrine functions independent of blockade of gastrin secretion. In order to further investigate this suppressive effect, somatostatin derivatives were injected to cats bearing a cannulated gastric fistula under pentagastrin stimulation. Results showed that somatostatin-14 was more potent than somatostatin-28 in this particular model. Analogues with substituted residues exhibited a variable spectrum of actions on hormone release and gastric function. A cyclic pentapeptide was deprived of gastric or GH inhibitory properties whereas the related peptide with a benzyl-protecting group on Thr was only devoid of gastric effect. The octapeptide SMS 201-995 was described as a potent inhibitor of gastric secretion in comparison with natural somatostatin in rats and also in humans, but was unable to induce maximal suppression of acid output in the cat model. Differences in gastric effect of different derivatives could be explained on the basis of binding to a selective subset of receptors, since at least two binding sites have been identified in the stomach mucosa. Serial studies with short cyclic somatostatin should help to establish a clear relationship between peptide structure and inhibition of gastric secretion.
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PMID:Somatostatin structure-activity studies in the stomach. 290 Feb 1

The tetradecapeptide somatostatin produced dose-related neurological deficits following subarachnoid injection in the lumbar spinal cords of rats. Lower pharmacological doses (1.6 and 3.1 nmol, i.t.) of somatostatin caused only transient deficits, while higher doses (6.2-25 nmol, i.t.) caused persistent deficits characterized by motor and sensory impairments in hindlimbs and tail, hindlimb edema, priapism, bladder atony with infarction, and urinary incontinence. Pretreatment with 0.3 nmol of the somatostatin receptor antagonist cyclo[7-aminoheptanoyl-Phe-D-Trp-Lys-Thr(Bzl)] blocked the hindlimb paralytic effects of 3.1 and 6.2 nmol of somatostatin, and significantly improved neurological recovery injection of 12.5 nmol of somatostatin. Higher doses of the antagonist produced hindlimb paralysis by itself. Neuroanatomical evaluations revealed extensive cell loss and necrosis in the lumbosacral spinal cords of rats paralyzed by 25 nmol of somatostatin. Collectively, these results suggest that through interactions with a receptor, somatostatin destroys neurons involved in diverse spinal cord functions.
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PMID:Spinal subarachnoid injection of somatostatin causes neurological deficits and neuronal injury in rats. 290 Jul 68


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