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 content of somatostatin-like immunoreactivity (SRIF-LI) and neuropeptide Y-like immunoreactivity (NPY-LI) has been measured in both control post-mortem human brains and in Huntington's disease brains. The content of both SRIF-LI and NPY-LI was found to be significantly increased in the basal ganglia of Huntington's disease brains compared with a control group. The nature of the SRIF-LI and NPY-LI in both control and Huntington's disease brains was investigated after separation on Sephadex G25 and G50 columns. Using a C-terminal-directed SRIF radioimmunoassay (RIA), 3 peaks of immunoreactivity were measured, whilst an N-terminal-directed SRIF RIA detected two peaks of immunoreactivity. In each case, the elution profile did not differ between control and Huntington's disease caudate nucleus. The content of immunoreactivity in each peak was found to be increased in Huntington's disease brains compared with controls. Only one peak of NPY-LI was detected in both control and Huntington's disease caudate after separation on Sephadex G25 and G50 columns. Immunohistochemical staining of the caudate and putamen of control and Huntington's disease brains revealed a population of neurones containing NPY-LI. The number of NPY-positive neurones was found to be increased in both the caudate and putamen of Huntington's disease brains compared to control caudate and putamen.
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PMID:Survival of basal ganglia neuropeptide Y-somatostatin neurones in Huntington's disease. 286 59

A radioiodinated analogue of somatostatin 28, 125I [Leu8,D-Trp22,Tyr25] SS-28, was used to localize and characterize somatostatin binding sites in both human and monkey brain. High-affinity binding sites (approximately 1 nM) were found in cerebral cortex. The highest binding was in cerebral cortex with intermediate binding found in hippocampus, striatum, and amygdala and low binding in hypothalamus and brainstem. There was a rough correlation between somatostatin receptor binding and concentrations of somatostatin-like immunoreactivity (SLI) in human brain. Somatostatin receptors were stable for up to 24 h in an animal model simulating human autopsy conditions and there was no correlation between postmortem interval and receptor binding in human brain. Pharmacologic characterization in human cortex showed that there was a correlation between the inhibition of receptor binding by somatostatin analogues and their known abilities to inhibit growth hormone secretion. These findings demonstrate that a highly specific membrane-associated receptor for somatostatin is present in both monkey and human brain. Examination of somatostatin receptor binding in Alzheimer's disease and Huntington's disease may improve understanding of the role of somatostatin in both these illnesses.
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PMID:Somatostatin binding sites in human and monkey brain: localization and characterization. 286 23

Huntington's disease is accompanied by severe neuronal death in the striatum, but despite this cell loss, there is a marked increase in the striatal concentration of somatostatin-like immunoreactivity (SLI). We attempted to examine the mechanism of this increase by using kainic or ibotenic acid to effect a unilateral lesion in the rat neostriatum. Graded doses of toxin cause a proportional decrease in the concentration of somatostatin-like immunoreactivity to a maximum of 50% of control, which is stable over an interval of 3 months. The increased somatostatin-like immunoreactivity in Huntington's disease is not mimicked by the excitotoxin lesions in rats. In addition we find that unilateral kainic acid lesions in the striatum reduce SLI in the contralateral striatum as well, although histologic evidence and assay of choline acetyltransferase activity indicate that damage is confined to the injected side. Immunocytochemistry demonstrates a loss of somatostatin-containing neurons on the lesioned side but no discernible loss in the contralateral striatum. The bilateral decrease in SLI following unilateral lesions suggests damage to a somatostatin projection to the contralateral striatum or a compensatory interaction between the two striatal nuclei.
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PMID:Excitotoxin lesions do not mimic the alteration of somatostatin in Huntington's disease. 286 8

Concentrations of somatostatin-like immunoreactivity (SLI) in CSF were reduced in Alzheimer's disease (AD) and multi-infarct dementia (p less than 0.01), but not in normal-pressure hydrocephalus, Parkinson's disease, and Huntington's disease. This suggests that reduced SLI content in AD cerebral cortex is reflected in CSF. Chromatographic characterization of CSF SLI showed no differences between AD and controls. Concentrations of SLI in AD patients overlapped those in both normal subjects and patients with multi-infarct dementia, so that changes in CSF SLI have no diagnostic specificity.
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PMID:CSF somatostatin-like immunoreactivity in dementia. 286 29

Somatostatin levels in the basal ganglia are elevated in Huntington's disease. A controlled therapeutic trial of the somatostatin-depleting agent, cysteamine, was therefore conducted in five patients, including one with the rigid-akinetic form. Maximum tolerated dosage for 2 weeks produced no consistent change in extrapyramidal or dementia scores. Somatostatin concentrations were not significantly altered in plasma or CSF. Growth hormone levels, on the other hand, more than doubled, suggesting a functionally significant decrease in central somatostatin levels.
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PMID:Huntington's disease: effect of cysteamine, a somatostatin-depleting agent. 287 27

Since its discovery, at the beginning of 1973, somatostatin's multiple actions, in relation to its wide anatomical distribution have been widely documented. Its biochemical pathways have been elucidated with the discovery of other molecular forms as well as the mechanisms of its neuronal release. However, no definite proof is available concerning a neurotransmitter role for any peptide of the somatostatin family other than somatostatin-14. The precise determination of the roles of somatostatin in brain are still hampered by the poor pharmacology of the peptide. New tools are badly needed and in particular a true antagonist at the receptor site. The mechanisms of action of somatostatin are now well under way at least in the pituitary model. More information should come from this model and be applied to brain cells in vitro. The greatest challenge of somatostatin brain function lies in its role in the pathophysiology of neurological diseases such as Alzheimer's dementia and Huntington's disease. Nature has been using somatostatin-related molecules since inhibitory control was first needed in cell functions. Time will tell us if somatostatin is really an old peptide involved in senile dementia.
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PMID:Somatostatin in the central nervous system: physiology and pathological modifications. 287 91

Intrastriatal injections of excitotoxic amino acids and their analogues (for example kainate and ibotenate) elicit a pattern of neuronal degeneration that is similar in many respects to that observed in Huntington's disease. In this disease there is a progressive degeneration of most types of intrinsic neuron but somatostatin and neuropeptide Y levels are increased 3-5-fold. This may be attributed to the selective preservation of a sub-class of striatal aspiny neurons, in which these two peptides are co-localized together with the enzyme NADPH-diaphorase. Beal et al. reported recently that following intrastriatal injections of quinolinic acid in rats, medium-sized aspiny neurons were selectively preserved and they suggested that quinolinic acid which is found in human brain might cause the neuronal degeneration seen in Huntington's disease. We have used immunocytochemical and enzyme histochemical techniques to examine this selective toxicity but find no evidence to support this finding. We conclude that there are substantial differences between the immunocytochemical changes detected in postmortem Huntington's disease brain and those following quinolinic-acid-induced degeneration.
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PMID:No evidence for preservation of somatostatin-containing neurons after intrastriatal injections of quinolinic acid. 288 69

Corticotropin-releasing hormone-like immunoreactivity (CRH-IR) was measured in control and Huntington's disease brain tissues obtained postmortem. The concentration of CRH-IR was markedly decreased in the caudate/putamen in Huntington's disease; the concentration of somatostatin-like immunoreactivity measured in the same extracts was significantly increased in the caudate/putamen in Huntington's disease compared with the control group. In contrast to previously reported decreases in CRH-IR in the cerebral cortex in Alzheimer's disease, Parkinson's disease and progressive supranuclear palsy, no significant differences were observed in the concentrations of CRH-IR between controls and Huntington's disease in frontal, parietal, temporal, occipital and cingulate cortex and in globus pallidus.
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PMID:Corticotropin-releasing hormone (CRH) is decreased in the basal ganglia in Huntington's disease. 289 55

Somatostatin and neuropeptide Y concentrations have previously been reported to be increased in the basal ganglia in Huntington's disease (HD). In the present study we have extended these findings by examining both somatostatin-like immunoreactivity (SLI) and neuropeptide Y-like immunoreactivity (NPYLI) in cases of HD, which were graded according to the severity of pathological degeneration in the striatum. In addition, we surveyed a large number of subcortical nuclei and cortical regions for alterations. Both SLI and NPYLI were significantly increased about threefold in the caudate, putamen, and the nucleus accumbens. Increases in mild and severe grades were similar, which is consistent with a relative but not absolute sparing of striatal aspiny neurons in which somatostatin and neuropeptide Y are colocalized. Significant increases of NPYLI were also found in the external pallidum, subthalamic nucleus, substantia nigra compacta, claustrum, anterior and dorsomedial thalamus, bed nucleus of the stria terminalis, and locus ceruleus. SLI was significantly increased in the external pallidum, red nucleus, and locus ceruleus. Measurements of both neuropeptides were made in 24 regions of the cerebral cortex. Significant increases in both NPYLI and SLI were found in the frontal cortex (Brodmann areas 6, 8, 9, 10, 11, and 45) and temporal cortex (Brodmann area 21), whereas NPYLI was also increased in Brodmann areas 12, 20-22, 25, and 42. Alterations in the cerebral cortex were as pronounced in cases with mild striatal pathological changes as in those with severe striatal pathological changes. These alterations may occur early in HD and could reflect a selective sparing of somatostatin-neuropeptide Y cortical neurons combined with cortical atrophy.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Somatostatin and neuropeptide Y concentrations in pathologically graded cases of Huntington's disease. 290 Jun 22

Somatostatin was originally isolated as a 14-amino-acid peptide from the ovine hypothalamus. The peptide has a widespread regional distribution within the central and peripheral nervous systems, as well as in peripheral organs. Preservation of the chemical structure over a wide range of vertebral species indicates important functional roles of the peptide. Recent results about the role of somatostatin and related peptides in different psychiatric (depression, schizophrenia, Alzheimer's disease) and neurological (Huntington's disease, multiple sclerosis, Parkinson's disease) diseases, and the effects on the hypothalamic-pituitary-adrenal axis are summarized. Also, the influence of some psychotropic drugs (halo-peridol, carbamazepine) on somatostatin levels in cerebrospinal fluid is discussed.
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PMID:Brain and CSF somatostatin concentrations in patients with psychiatric or neurological illness. An overview. 290 14


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