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 new long-acting octapeptide analogue of somatostatin, Des AA1,2,4,5,12,13 D Try8 somatostatin, has been tested in 8 patients with pancreatic endocrine tumours. The analogue given subcutaneously suppressed the tumour-derived hormones in patients with insulinomas, glucagonomas, and gastrinomas for up to 24 h. The prolonged action appeared to be the result of slow release from the injection site. No side-effects were observed. Studies of long-term administration of this new peptide are now warranted.
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PMID:Suppression of pancreatic endocrine tumour secretion by long-acting somatostatin analogue. 9 Aug 60

Somatostatin (SRIF) has been tested for its actions on the central nervous system to affect glucoregulation. In doses ineffective when given systemically , SRIF and SRIF analogs given intracisternally (ic) reduce hyperglycemia and hyperglucagonemia after ic bombesin administration. The SRIF analog, des-AA1, 2, 4, 5, 12, 13-[D-Trp8]SRIF, decreases plasma insulin and elevates plasma glucose and glucagon when given systemically. However, when given ic, this peptide prevents the rise in glucose and glucagon after ic bombesin administration and is 10 times more potent than SRIF in reducing bombesin-induced hyperglycemia. Other analogs of SRIF and various unrelated peptides were found to be ineffective in reducing bombesin-induced hyperglycemia. des-AA1, 2, 4, 5, 12, 13-[D-Trp]SRIF prevented the hyperglycemia induced by surgical stress or by ic administration of beta-endorphin or carbacol. des-AA1, 2, 4, 5, 12, 13-[D-Trp]SRIF given ic did not prevent hyperglycemia induced by systemic administration of epinephrine, arginine, or glucagon. These studies suggest that SRIF and its analogs may act within the brain to affect glucoregulation.
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PMID:Somatostatin: central nervous system actions on glucoregulation. 44 91

We previously found that quinolinic acid striatal excitotoxin lesions result in a relative sparing of somatostatin and neuropeptide Y neurons. In the present study we examined dose-response effects of excitotoxins acting at the three subtypes of glutamate receptors: N-methyl-D-aspartate (AA1), quisqualate (AA2), and kainic acid (AA3). Concentrations of both somatostatin-like immunoreactivity (SLI) and neuropeptide a Y-like immunoreactivity (NPYLI) were compared with those of substance P-like immunoreactivity (SPLI) and GABA. Kainic acid (AA3), quisqualic acid (AA2), and AMPA (AA2) resulted in dose-dependent reductions in all four neurochemical markers examined, while N-methyl-D,L-aspartate (AA1) and quinolinic acid (AA1) resulted in relative sparing of SLI and NPYLI. At doses of each excitotoxin which resulted in comparable 50% reductions in both GABA and SPLI only N-methyl-D,L-aspartate and quinolinic acid had no significant effect on concentrations of SLI and NPYLI. The relative sparing of somatostatin-neuropeptide Y neurons was confirmed histologically by using histochemical staining for NADPH-diaphorase neurons combined with either Nissl stains, or immunohistochemical staining for enkephalin. Lesions with N-methyl-D-aspartate agonists resulted in preferential sparing of NADPH-diaphorase neurons while these neurons were more vulnerable than other neurons to kainic acid or AMPA. Choline acetyltransferase neurons were relatively spared, as compared with other neurons, by agents acting at all three glutamate receptor subtypes. N-methyl-D,L-aspartate lesions were blocked with MK-801, while there was no effect on quisqualic acid or kainic acid lesions. The relative sparing of somatostatin-neuropeptide Y neurons following striatal excitotoxin lesions with N-methyl-D-aspartate (AA1) agonists probably reflects a paucity of AA1 receptors on these neurons. Since these neurons are also spared in Huntington's disease, excitotoxins acting at the N-methyl-D-aspartate (AA1) site provide an improved neurochemical model of this illness.
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PMID:Differential sparing of somatostatin-neuropeptide Y and cholinergic neurons following striatal excitotoxin lesions. 256 16

In the present study the effects of somatostatin and its analogs on active avoidance behavior, electroconvulsive shock (ECS)-induced retrograde amnesia, and spatial-discrimination learning were compared in rats. (D-Trp8, D-Cys14)-somatostatin (as did the somatostatin molecule itself) delayed the extinction of active avoidance behavior, antagonized ECS-induced amnesia, and did not modify spatial-discrimination learning. Des-Asn5-(D-Trp8, D-Ser13) somatostatin and des-AA1,2,4,5,12,13,-(D-Trp8) somatostatin did not influence these behaviors. The data suggest that certain parts of the somatostatin molecule are important for its behavioral actions.
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PMID:Somatostatin and (D-Trp8, D-Cys14)-somatostatin delay extinction and reverse electroconvulsive shock induced amnesia in rats. 287 76

Somatostatin binding to guinea pig pancreatic acinar cell plasma membranes was characterized with an iodinated stable analog of somatostatin 28 (S28): 125I-[Leu8,DTrp22,Tyr25]S28. The binding was highly dependent on calcium ions. In 0.2 mM free Ca2+ medium, binding at 37 degrees C was saturable, slowly reversible and exhibited a single class of high affinity binding sites (KD = 0.05 +/- 0.01 nM, Bmax = 157 +/- 33 fmol/mg protein). Dissociation of bound radioactivity occurred with biphasic kinetics. Rate of dissociation increased when dissociation was measured at a time before equilibrium binding was reached. In 30 nM free Ca2+ medium, binding affinity and maximal binding capacity were decreased by about 4-fold. Decreasing calcium concentrations increased the amount of rapidly dissociating form of the receptor. Somatostatin 14 antagonist, Des AA1,2[AzaAla4-5,DTrp8, Phe12-13]-somatostatin was active at the membrane level in inhibiting the binding. We conclude that using 125I-[Leu8,DTrp22,Tyr25]S28 as radioligand allows us to characterize a population of specific somatostatin receptors which are not different from those we previously described with the radioligand 125I-[Tyr11]-somatostatin. Somatostatin receptors could exist in two interconvertible forms. Calcium ions are an essential component in the regulation of the conformational change of somatostatin receptors.
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PMID:Characterization of pancreatic somatostatin binding sites with a 125I-somatostatin 28 analog. 288 95

The distribution of high-affinity binding sites for [3H]somatostatin has been studied in membrane preparations from a number of regions of normal human brain. The highest densities of binding sites (greater than 48 fmol/mg protein) were found in the cerebral and cerebellar cortices and the hippocampus, with intermediate binding densities (30-46 fmol/mg protein) being present in the basal ganglia, amygdala, septum and claustrum. The lowest densities of binding sites (less than 14 fmol/mg protein) were observed in the hypothalamus, thalamus and substantia nigra. The binding of [3H]somatostatin in both the frontal cortex and cerebellar cortex demonstrated pharmacological specificity, since somatostatin-28, but not somatostatin-28(1-12) or Des AA1,2,4,5,12,13, D-Trp8-somatostatin, competed for the binding sites. Scatchard analysis of the binding in both frontal cortex and cerebellar cortex revealed the presence of two classes of high-affinity binding sites.
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PMID:Regional distribution of high-affinity [3H]somatostatin binding sites in the human brain. 302 63

The somatostatin analog, des-AA1,2,4,5,12,13-[D-Trp8]somatostatin (ODT8-SS), acts within the central nervous system to suppress the rise in plasma catecholamines associated with a variety of neural stimuli. Insulin-induced hypoglycemia or stress caused significant elevations in plasma catecholamines that were abolished by intracerebroventricular (icv) administration of ODT8-SS. Bombesin, carbachol, or 2-deoxyglucose, injected icv, evoked marked elevations in plasma epinephrine and norepineprine. These effects were also prevented by ODT8-SS given icv. In all experiments, ODT8-SS appeared to be more effective in lowering plasma epinephrine than in lowering plasma norepinephrine. Systemic administration of ODT8-SS was ineffective in lowering plasma catecholamine levels. Native somatostatin given icv produced inconsistent effects on plasma catecholamine levels. These data suggest that the somatostatin analog, ODT8-SS, acts within the central nervous system to modulate sympathetic nervous system activity. It is suggested, but not established, that this analog acts through the same receptor as native somatostatin.
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PMID:Somatostatin analog: plasma catecholamine suppression mediated by the central nervous system. 610 69

We have recently demonstrated the presence of specific receptors for somatostatin (SRIF) in rat brain synaptosomal membranes which appear to mediate its action. Using this system as a radioreceptor assay, we have examined the ability of a wide range of SRIF analogs to interact with these receptors. Although structural modifications in the Trp8 moiety of SRIF resulted in significant enhancement of affinity for binding to the brain SRIF receptors, the different relative specificities of des AA1,2,4,5,12,13 D-Trp8 SRIF (oligo D-Trp8 SRIF), D-Trp8 SRIF and D-5-Br-Trp8 SRIF in the pituitary and the central nervous system (CNS) suggest that basic differences exist between SRIF receptors present in the brain and the pituitary.
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PMID:Somatostatin analogs. Dissociation of brain receptor binding affinities and pituitary actions in the rat. 610 22

Intracisternal injection of octapeptide analogs of somatostatin (SS), Cys-Phe-Phe-D-Trp-Lys-Thr-Phe-Cys (des-AA1,2,4,5,12,13-[D-Trp8]SS (ODT8-SS)) and Cys-Phe-Phe-D-Trp-Lys-Thr-Phe-D-Cys, increased the volume and the acid output of gastric secretion in rats. ODT8-SS given intravenously did not affect basal gastric secretion. The gastrosecretory effect of ODT8-SS, administered intracisternally is dose-dependent (0.01-1 micrograms), long acting, reversible, specific, and abolished by vagotomy, or systemic injection of atropine or SS. SS (5-10 micrograms) or [D-Trp8]SS (1 microgram) had no effect on gastric secretion when given intracisternally. These results demonstrate that some octapeptide SS analogs, unlike SS or other SS analogs, have the capability to act in the brain to induce a vagal dependent stimulation of gastric secretion.
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PMID:Is somatostatin or a somatostatin-like peptide involved in central nervous system control of gastric secretion? 611 19

During a control infusion noradrenaline and alcohol each provoked carcinoid flushing in four of five patients and pentagastrin in two of five patients. When tetradecapeptide somatostatin was infused on another day no patient flushed at any time, even when 16 microgram of either noradrenaline or pentagastrin were administered. Carcinoid flushing was not associated with release of gastrin or any of the other vasoactive or postprandially released gut regulatory peptides measured. In a sixth patient with severe prolonged carcinoid flushing, subcutaneous Des AA1, 2, 4, 5, 12D Trp8 somatostatin markedly reduced the incidence and severity of flushing for two days. Somatostatin is thus a potent inhibitor of carcinoid flushing, but no evidence has been found for the gut hormones measured to be mediators of flushing.
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PMID:Somatostatin, gastrointestinal peptides, and the carcinoid syndrome. 611 1


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