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)

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

Two-color immunofluorescence histochemistry and immunohistochemistry in combination with retrograde tract-tracing techniques were used to examine the relationship of alpha-amino-3-hydroxy-5-methyl-4-isoxazole proprionic acid (AMPA)-selective glutamate receptor subunits (GluR1, GluR2/3/4c and GluR4) to identified populations of striatal projection neurons and interneurons. The majority of striatonigral and striatopallidal neurons were double-labeled for GluR2/3/4c. These findings were confirmed using calbindin to label matrix projection neurons. In contrast, immunostaining of the GluR1 subunit was not observed to co-localize with any striatal projection neurons. Striatal interneurons immunostained for parvalbumin were also labeled by antibodies directed against the GluR1 subunit. Approximately 50% of parvalbumin neurons also contained GluR2/3/4c. Somatostatin immunoreactivity did not co-localize with either the GluR1 or GluR2/3/4c subunits. GluR4-immunoreactive neurons were not observed in striatum. This study demonstrates that AMPA-selective glutamate receptors are differentially localized on subpopulations of striatal neurons and interneurons. These findings suggest that discrete striatal neuron populations may express different AMPA receptor subunit combinations which may account for their functional specificity.
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PMID:Localization of AMPA-selective excitatory amino acid receptor subunits in identified populations of striatal neurons. 796 27

L-Glutamate, NMDA, DL-alpha-amino-3-hydroxy-5-methyl-4-isoxazole propionate (AMPA), and kainate (KA) increased the release of somatostatin-like immunoreactivity (SRIF-LI) from primary cultures of rat hippocampal neurons. In Mg(2+)-containing medium, the maximal effects (reached at approximately 100 microM) amounted to 737% (KA), 722% (glutamate), 488% (NMDA), and 374% (AMPA); the apparent affinities were 22 microM (AMPA), 39 microM (glutamate), 41 microM (KA), and 70 microM (NMDA). The metabotropic receptor agonist trans-1-aminocyclopentane-1,3-dicarboxylate did not affect SRIF-LI release. The release evoked by glutamate (100 microM) was abolished by 10 microM dizocilpine (MK-801) plus 30 microM 1-aminophenyl-4-methyl-7,8-methylenedioxy-5H-2,3-benzodiazepine (GYKI 52466). Moreover, the maximal effect of glutamate was mimicked by a mixture of NMDA+AMPA. The release elicited by NMDA was sensitive to MK-801 but insensitive to GYKI 52466. The AMPA- and KA-evoked releases were blocked by 6,7-dinitroquinoxaline-2,3-dione (DNQX) or by GYKI 52466 but were insensitive to MK-801. The release of SRIF-LI elicited by all four agonists was Ca(2+) dependent, whereas only the NMDA-evoked release was prevented by tetrodotoxin. Removal of Mg2+ caused increase of basal SRIF-LI release, an effect abolished by MK-801. Thus, glutamate can stimulate somatostatin release through ionotropic NMDA and AMPA/KA receptors. Receptors of the KA type (AMPA insensitive) or metabotropic receptors appear not to be involved.
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PMID:Characterization of the glutamate receptors mediating release of somatostatin from cultured hippocampal neurons. 852 49

Glutamate receptors are composed of subtype-specific subunits. Variation in the precise subunit composition of a receptor may result in significant functional differences. Thus, a precise knowledge of subunit composition on striatal neurons is a prerequisite for understanding the selective vulnerability of striatal neurons to excitatory amino acids. In the present study, we used an immunohistochemical double-labelling approach to localize ionotropic glutamate receptor subunits (NMDAR1, GluR1, GluR2/3, GluR4 and GluR5/6/7) on specific striatal neuron populations. Our results showed that striatal cholinergic and somatostatin interneurons were not labelled for the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionate, receptor subunits GluR1, GluR2/3 and GluR4. Most cholinergic and somatostatin interneurons (83.3% to 100%), however, were double-labelled for the N-methyl-D-aspartate receptor subunit NR1 and kainic acid receptor subunits GluR5/6/7. All parvalbumin interneurons were labelled for GluR1 and GluR4, and 96% GluR1 positive and 95% GluR4 positive neurons were also double-labelled as parvalbumin interneurons. About half of all parvalbumin interneurons co-localized with GluR2/3, and over 97% were labelled for NR1 and GluR5/6/7. Among striatal projection neurons, enkephalin-positive (mainly striatopallidal) neurons, striatonigral neurons (mainly substance P-positive) and calbindin-positive matrix neurons were not immunostained for GluR1 or GluR4. In contrast, 95% to 100% of each of these types of projection neurons were double-labelled for NR1, GluR2/3 and GluR5/6/7. Our results demonstrate that striatal neuron types differ in their expression of ionotropic glutamate receptor subunits and subtypes. The clear difference between striatal interneurons and projection neurons in ionotropic glutamate receptor subtypes/subunits supports the idea that differential glutamate receptor expression mechanism may account for the selective vulnerability of striatal projection neurons to excitotoxicity, and that glutamate receptor-mediated excitotoxicity may be involved in the striatal neurodegenerative diseases.
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PMID:Cellular expression of ionotropic glutamate receptor subunits on specific striatal neuron types and its implication for striatal vulnerability in glutamate receptor-mediated excitotoxicity. 880 93

The alpha-amino-3-hydroxy-5-methyl-4-isoxazole (AMPA) receptor antagonist, 2,3-dihydroxy-6-nitro-7-sulfamoyl-benzo(F)quinoxaline (NBQX), offers protection to hippocampal CA1 pyramidal cells after short episodes of transient cerebral ischemia. Besides CA1 pyramidal cells, neurons containing somatostatin (SS) and located in the dentate hilus of the hippocampal formation are lost after cerebral ischemia. We studied the protective effects of NBQX on SS neurons in the hilus and on hippocampal CA1 pyramidal cells following 8, 10, or 12 min of four-vessel occlusion ischemia during systemic hypotension. NBQX was administered 3 x 30 mg/kg at 0, 10, and 25 after induction of ischemia or sham, and all rats survived for 7 days. NBQX given to control rats without ischemia had no influence on number or morphology of hilar SS neurons and CA1 pyramidal cells. After 8 min of ischemia, NBQX prevented loss of hilar SS neurons. After 10 and 12 min of ischemia, NBQX had no significant effects on loss of SS neurons in the dentate hilus. However, in all ischemic groups, NBQX significantly reduced loss of CA1 pyramidal cells as compared to control rats. This neuroprotective effect decreased gradually and significantly as the time of ischemia increased. Our results support the observation that SS neurons in hilus are among the most ischemia-vulnerable neurons in the brain. We found that administration of NBQX in generally accepted dosages can protect the rapidly dying SS neurons in hilus from only brief episodes of ischemia.
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PMID:Effects of the AMPA-receptor antagonist, NBQX, on neuron loss in dentate hilus of the hippocampal formation after 8, 10, or 12 min of cerebral ischemia in the rat. 904 Apr 93