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)

Growth hormone regulation was studied in 10 patients with Huntington's disease after intravenous administration of arginine. In 20 control subjects arginine infusion resulted in a rise of plasma growth hormone levels from a mean baseline value of 3.2+/-0.6 ng/ml to a peak level of 17.6+/-2.7 ng/ml at 60 min. Growth hormone rise in the majority of patients with Huntington's disease was clearly intact and significantly greater than normal in magnitude, increasing from the baseline level of 2.6+/-0.5 ng/ml to a peak level of 28.3+/-3.7 ng/ml at 60 min (P = less than 0.05). Carbohydrate tolerance of these patients was previously examined, and 4 with normal glucose tolerance and normal insulin responses to arginine infusion had growth hormone levels significantly higher than controls at 30 min. Six patients with impaired carbohydrate tolerance and exaggerated insulin responses to arginine had significantly higher growth hormone responses at 30 min and also at 60 min. Neuronal degeneration of several hypothalamic nuclei has been reported in Huntington's disease. The observations that growth hormone responds in an exaggerated fashion to stimulation by arginine infusion or falling glucose levels as previously described may be explained by intrahypothalamic dysfunction such as impairment of somatostatin secretion.
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PMID:Exaggerated growth hormone response to arginine infusion in Huntington's disease. 12 87

Huntington's disease is a progressive neurodegenerative disease in which the basal ganglia are preferentially affected. Recent evidence, however, suggests involvement of the cerebral cortex as well, with sparing of neurochemically defined subsets of gamma-aminobutyric acid (GABA)-ergic interneurons. In the present study, we examined changes in concentrations of the amino acid neurotransmitters GABA, glutamate, and aspartate in nine cortical regions from 23 patients with advanced Huntington's disease and 12 control brains. GABA concentrations were significantly increased in eight of the nine regions, consistent with a sparing of GABAergic local circuit neurons in the context of progressive cortical atrophy. Small but significant increases in glutamate were found in six of the nine regions, while aspartate levels were generally unaffected. Striate cortex (Brodmann's area 17) showed the most profound increases in GABA and glutamate. We also investigated the effects of powdering the excitotoxins N-methyl-D-aspartate (NMDA) or kainic acid onto the dura of rats. The resulting lesions were examined at 1 week and 6 months. The NMDA-induced lesions showed striking sparing of parvalbumin-positive neurons (a subset of GABAergic interneurons), and this sparing was reflected in neurochemical measurements of GABA; kainic acid lesions failed to display this selectivity. Somatostatin, cholecystokinin, and vasoactive intestinal polypeptide concentrations were spared by the NMDA-induced lesions, and substance P levels were significantly increased. These results provide evidence that NMDA excitotoxic lesions of cerebral cortex can produce a selective pattern of neuronal damage similar to that which occurs in Huntington's disease.
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PMID:The cortical lesion of Huntington's disease: further neurochemical characterization, and reproduction of some of the histological and neurochemical features by N-methyl-D-aspartate lesions of rat cortex. 128 Sep 37

Somatostatin (somatotropin release-inhibiting factor, SRIF) was originally discovered (1) during the purification of growth hormone-releasing factor from rat hypothalamus and was subsequently isolated and characterized (2) in 1972 from ovine hypothalamus. Since its initial characterization, SRIF has been shown to fulfill criteria for a neurotransmitter and to directly modulate neuronal activity as well as acting as an inhibitory factor regulating endocrine and exocrine secretion. Alterations in cerebrospinal fluid (CSF) concentrations of SRIF have been reported in several diseases exhibiting prominent cognitive dysfunction, including Alzheimer's disease (AD), major depression, Huntington's chorea, multiple sclerosis, schizophrenia and Parkinson's disease, while evidence for regional brain tissue concentration deficits in SRIF are more specific for AD. This mini-review will focus on the studies reporting alterations in CSF and postmortem tissue concentrations of SRIF in AD and depression.
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PMID:Somatostatin in Alzheimer's disease and depression. 135 21

The lateral tuberal nucleus is a circumscribed cell mass in the lateral posterior part of the hypothalamus, containing about 60000 neurons. It can be recognized in man and higher primates, probably not in other mammals. Its neurotransmitter content and connections with other parts of the brain are as yet unknown. But receptors for corticotropin-releasing factor and somatostatin, as well as muscarinic cholinergic receptors, benzodiazepine receptors and N-methyl-D-aspartate receptors have been localized within the confines of the nucleus. The lateral tuberal nucleus is affected in a number of human neurodegenerative diseases. Changes in Parkinson's disease are the least obvious: Lewy bodies appear in small amounts, the majority of them apparently lying outside a neuronal perikaryon. Neuronal loss does not occur. In Alzheimer's disease the number of neurons seems to be normal as well. Rarely silver staining tangles occur, and the deposition of A4/beta-protein in amorphous plaques is moderate. Yet, NTL neurons stain heavily in Alz-50 immunocytochemistry, while Alz-50 staining in NTL neurites is very dense. These changes are interpreted as indicating early Alzheimer-related pathology. In Huntington's disease the NTL loses neurons. This loss is related to the severity of the disease: patients who first display motor disturbances at an early age will lose more neurons than those who start later. The relation between these clinical characteristics and the severity of neuronal loss is such, that it seems likely that NTL neurons possess a special vulnerability for the effect of the Huntington gene. This could be related to their NMDA-receptor content. It is hypothesized that the NTL is involved in a neuronal network that regulates feeding and metabolism. NTL pathology may explain the peculiar catabolic state of many patients with Alzheimer's or Huntington's diseases.
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PMID:The hypothalamic lateral tuberal nucleus: normal anatomy and changes in neurological diseases. 136 79

The intrastriatal infusion of relatively low doses of quinolinic acid (Quin, 4-10 nmol/h) for 1 or 2 weeks induced time-dependent degeneration of neuronal cells. We examined the effects of these infusions on discrete cellular populations. The distribution of somatostatin (SOM)-positive neurons labelled by immunocytochemistry or by NADPH-diaphorase histochemistry and of cholinergic cells stained by acetylcholinesterase was quantified in the peripheral portion of the lesioned area. SOM-positive cells did not appear selectively spared by Quin infusion. The proportion of SOM- and NADPH-diaphorase-positive neurons killed by exposure to Quin was similar to or higher than the percentage of total neurons degenerated (from 30 to 85%). A selective sparing of cholinergic cells was observed in all conditions examined; perfusion of 6 nmol/h for a week induced 65% of cell death while not more than 30% of cholinergic neurons were killed. Thus, the neurochemical similarity between the degenerative effects of intrastriatal Quin and Huntington's disease (HD) did not appear confirmed by the chronic perfusion of low doses of Quin for SOM-positive neurons, whereas an analogy between Quin's effects and HD was suggested by the pattern of AChE staining.
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PMID:Chronic infusion of quinolinic acid in rat striatum: effects on discrete neuronal populations. 138 77

Neuronal degeneration that occurs in both ischemia and degenerative neurologic illnesses may involve excitotoxic mechanisms. In the present study, we examined whether cortical lesions with agonists acting at subtypes of glutamate receptors result in selective patterns of neuronal death. Injections of quinolinic acid, NMDA, homocysteic acid, kainic acid (KA), and alpha-amino-3-hydroxy-5-methylisoxazole-4-proprionic acid (AMPA) were made at 2 sites in the dorsolateral frontoparietal cortex in rats. After 1 week, the cerebral cortex was either dissected for neurochemical studies, or animals were perfused for histologic evaluation. Concentrations of somatostatin (SS), neuropeptide Y (NPY), substance P (SP), cholecystokinin (CCK), and vasoactive intestinal polypeptide (VIP) were measured by radioimmunoassay, while amino acids and catecholamines were measured by high-performance liquid chromatography (HPLC) with electrochemical detection. NMDA agonists (quinolinic acid, homocysteic acid, and NMDA itself) resulted in dose-dependent reductions in glutamate and GABA, while SS, NPY, SP, CCK, and VIP were either unchanged or significantly increased in concentration. KA and AMPA at doses that resulted in comparable GABA depletions caused significant reductions in SS concentrations. Markers of cortical afferents were spared. All excitotoxins resulted in dose-dependent marked increases in uric acid concentrations. Histologic examination verified that lesions with NMDA agonists produced relative sparing of NADPH-diaphorase, SS, VIP, and CCK neurons. These results show that NMDA excitotoxin lesions result in a pattern of selective neuronal damage in the cerebral cortex that is similar to that which occurs in both ischemia and Huntington's disease.
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PMID:Neurochemical characterization of excitotoxin lesions in the cerebral cortex. 167 Jul 82

Striatal atrophy in Huntington's disease (HD) is characterized by selective preservation of a subclass of neurons colocalizing NADPH-diaphorase (NADPH-d), somatostatin (SS), and neuropeptide Y (NPY), which have been reported to show three- to fivefold increases in SS-like immunoreactivity (SSLI) and NPY content. Since HD brain is capable of producing excessive quantities of the excitotoxin quinolinic acid (Quin), an N-methyl-D-aspartate (NMDA) receptor agonist, and since experimental Quin lesions show neuronal loss with sparing of NADPH-d/SS/NPY neurons, it has been suggested that Quin may be important in the pathogenesis of HD. In the present study we determined whether Quin stimulates SS gene function in cultured cortical cells known to be rich in NADPH-d/SS/NPY neurons. Cultures of dispersed fetal rat cortical cells were exposed to Quin (1 and 10 mM) with or without (-)-2-amino-5-phosphonovaleric acid (APV; 0.5 mM), an NMDA receptor antagonist, NMDA (0.2 and 0.5 mM), and glutamate (Glu; 0.5 mM). Medium and cellular SSLI was determined by radioimmunoassay and SS mRNA by Northern analysis with a cRNA probe. Quin induced significant (p less than 0.01) 1.6- and 2.5-4 fold increases in SSLI and SS mRNA accumulation, respectively, which were abolished by APV. Release of SSLI into the culture medium was stimulated two- to fivefold by Quin over a 2- to 20-h period. The increase in SS mRNA produced by Quin was time and dose dependent. A similar dose-dependent increase in SS mRNA comparable with that observed with Quin was induced by NMDA.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Quinolinic acid stimulates somatostatin gene expression in cultured rat cortical neurons. 167 45

L-Homocysteic acid (L-HCA) is a sulfated amino acid which is present in mammalian striatum and is a putative excitatory striatal neurotransmitter. In the present study we examined the histologic and neurochemical effects of L-HCA induced striatal lesions to determine how closely changes resemble those of Huntington's disease (HD). Increasing doses of L-HCA injected into the anterior striatum resulted in dose-dependent reductions in both substance P-like immunoreactivity (SP-LI) and gamma-aminobutyric acid (GABA) while there was a relative sparing of both somatostatin-like immunoreactivity (SS-LI) and neuropeptide Y-like immunoreactivity (NPY-LI). Immunocytochemical studies showed a relative sparing of NADPH-diaphorase neurons (which colocalize with SS and NPY) within regions in which there was a significant depletion of enkephalin stained neurons. The lesions were blocked by pretreatment with MK-801, a systemically effective non-competitive antagonist of N-methyl-D-aspartate (NMDA) receptors or coinjection of equimolar concentrations of 2-amino-5-phosphonovalerate (APV). These findings are similar to those produced with the NMDA agonist quinolinic acid, and suggest that other endogenous NMDA agonists, such as L-HCA, could be potential excitotoxins in HD.
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PMID:Homocysteic acid lesions in rat striatum spare somatostatin-neuropeptide Y (NADPH-diaphorase) neurons. 168 75

We previously found a relative sparing of somatostatin and neuropeptide Y neurons 1 week after producing striatal lesions with NMDA receptor agonists. These results are similar to postmortem findings in Huntington's disease (HD), though in this illness there are two- to threefold increases in striatal somatostatin and neuropeptide Y concentrations, which may be due to striatal atrophy. In the present study, we examined the effects of striatal excitotoxin lesions at 6 months and 1 yr, because these lesions exhibit striatal shrinkage and atrophy similar to that occurring in HD striatum. At 6 months and 1 yr, lesions with the NMDA receptor agonist quinolinic acid (QA) resulted in significant increases (up to twofold) in concentrations of somatostatin and neuropeptide Y immunoreactivity, while concentrations of GABA, substance P immunoreactivity, and ChAT activity were significantly reduced. In contrast, somatostatin and neuropeptide Y concentrations did not increase 6 months after kainic acid (KA) or alpha-amino-3-hydroxy-5-methyl-isoxazole-4-propionic acid (AMPA) lesions. At both 6 months and 1 yr, QA lesions showed striking sparing of NADPH-diaphorase neurons as compared with both AMPA and KA lesions, neither of which showed preferential sparing of these neurons. Long-term QA lesions also resulted in significant increases in concentrations of both 5-HT and 5-hydroxyindoleacetic acid (HIAA), similar to findings in HD. Chronic QA lesions therefore closely resemble the neurochemical features of HD, because they result in increases in somatostatin and neuropeptide Y and in 5-HT and HIAA. These findings strengthen the possibility that an NMDA receptor-mediated excitotoxic process could play a role in the pathogenesis of HD.
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PMID:Chronic quinolinic acid lesions in rats closely resemble Huntington's disease. 171 Jun 57

This review summarizes the revolutionary impact of brain peptides on our understanding of the nervous system and then discusses the localization, distribution, synthesis, receptor sites, and possible function of 32 brain peptides. The peptides are discussed in three subgroups: I) the opioid peptides, which include beta-endorphin, the enkephalins, and dynorphin; II) the pituitary releasing hormones, most of which are wide-spread in the brain and include corticotropin-releasing hormone, luteinizing hormone-releasing hormone, somatostatin, and thyrotropin-releasing hormone; and III) a selection of 12 other peptides potentially important for neurological function, including vasopressin, oxytocin, substance P, cholecystokinin, bombesin, neurotensin, renin, angiotensin, vasoactive intestinal polypeptide, neuropeptide Y, calcitonin gene-related peptide, and calcitonin. Within each individual peptide section, the possible physiological roles in anterior pituitary hormone release, blood-flow regulation, feeding behavior, temperature regulation, nociception, memory and learning, and movement are reviewed. Further, where noted, the peptide findings in Huntington's, Alzheimer's, Parkinson's and psychiatric diseases are emphasized.
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PMID:Neuropeptides. 187 Jul 24


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