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)

Biochemical assays on microdissected samples, denervation studies, subcellular fractionation, and light and electron microscopic autoradiography of high affinity uptake have been performed to study the cellular localization of transmitter candidates in the rat hippocampal formation. High affinity uptake of glutamate and aspartate is localized in the terminals of several excitatory systems, such as the entorhino-dentate fibres (perforant path), mossy fibres (from granular cells) and pyramidal cell axons. Thus, in stratum radiatum and oriens of CA1, 85% of glutamate and asparate uptake and 40% of glutamate and aspartate content are lost after lesions of ipsilateral plus commissural fibres from CA3/CA4. Hippocampal efferents also take up aspartate and glutamate, since these activities are heavily reduced in the lateral septum and mamillary bodies after transection of fimbria and the dorsal fornix. The synthesis (by glutamic acid decarboxylase), content and high affinity uptake of gamma-aminobutyrate (GABA) are not reduced after lesions of these or other projection fibre systems. A localization in intrinsic neurons is confirmed by a selective loss of glutamic acid decarboxylase after local injections of kainic acid. Peak concentrations of the enzyme occur near the pyramidal and granular cell bodies, corresponding to the site of the inhibitory basket cell terminals, and in the outer parts of the molecular layers. Some 85% of glutamic acid decarboxylase is situated in 'nerve ending particles'. Acetylcholine synthesis (by choline acetyltransferase) disappears after lesions of septo-hippocampal fibres. Since 80% of the hippocampal choline acetyltransferase is in 'nerve ending particles', the characteristic topographical distribution of this enzyme should reflect the distribution of cholinergic septo-hippocampal afferents. Serotonin, noradrenaline, dopamine and histamine are located/synthesized in afferent fibre systems. Some monoamine-containing afferents to the hippocampal formation pass via the septal area, others via the amygdala. The hippocampal formation also contains nerve elements reacting with antibodies against neuroactive peptides, such as enkephalin, substance P, somatostatin and gastrin/cholecystokinin.
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PMID:Localization of putative transmitters in the hippocampal formation: with a note on the connections to septum and hypothalamus. 3 19

The pattern of hippocampal cell death has been studied following hippocampal seizure activity and status epilepticus induced by 110-min stimulation of the perforant pathway in awake rats. The order of vulnerability of principal cells in the different hippocampal subfields--as determined by silver impregnation--was found to be very similar to the pattern found in ischemia; i.e., dentate hilus greater than CA1, subiculum greater than CA3c greater than CA3a,b greater than dentate granule cells. The hilar somatostatin-containing cells were the most vulnerable cell type, whereas all other subpopulations of nonprincipal neurons--visualized by immunocytochemistry for the calcium binding proteins parvalbumin and calbindin--were remarkably resistant. Pyramidal cells in the CA3 region containing neither of the examined calcium binding proteins were more resistant to overexcitation than CA1 pyramidal cells, most of which do contain calbindin. This indicates that no simple relationship exists between vulnerability in status epilepticus and neuronal calcium binding protein content, and that local and/or systemic hypoxia during status epilepticus may be responsible for the ischemic pattern of cell death.
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PMID:Pattern of neuronal death in the rat hippocampus after status epilepticus. Relationship to calcium binding protein content and ischemic vulnerability. 134 49

The neuronal distributions of somatostatin and neuropeptide Y and their respective mRNAs in hippocampal slice cultures were examined by immunohistochemical staining and in situ hybridization. For the in situ hybridization we used an alkaline phosphatase-labelled oligodeoxynucleotide probe for somatostatin mRNA and an 35S-labelled oligodeoxynucleotide probe for neuropeptide Y mRNA. For both neuropeptides the immunostained and hybridized neurons displayed a comparable, organotypic distribution. Most labelled neurons were located in the dentate hilus and stratum oriens of CA3 and CA1. Additional neurons were found in stratum radiatum and pyramidale of CA3, but very few in the corresponding layers of CA1. In all locations the density of somatostatin- and neuropeptide Y-reactive cells exceeded that observed in vivo. Also, the hybridization signal of the individual neurons appeared enhanced in the slice cultures. Methodologically it was noted that the non-radioactive alkaline phosphatase-labelled oligodeoxynucleotide probe gave excellent in situ hybridization results with detailed cellular resolution and no apparent problems of tissue penetration, even when used on whole-mount explants. These results demonstrate that somatostatin and neuropeptide Y-immunoreactive and mRNA containing neurons retain their organotypic distribution and basic morphological characteristics in the slice cultures. The supernormal density of these neurons and their hybridization signals indicate that a transient developmental increase in neuropeptide expression may persist in vitro.
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PMID:Somatostatin and neuropeptide Y in organotypic slice cultures of the rat hippocampus: an immunocytochemical and in situ hybridization study. 134 30

Somatostatin receptors on lactotroph cells of the anterior pituitary are positively regulated by estradiol. In the present work, we investigated whether estradiol regulation of somatostatin receptors also occurred in the female rat brain. 125I-Tyr0-DTrp8-somatostatin (125I-SRIF: 780 Ci/mM) was used as a ligand. Female adult rats were ovariectomized and treated or not with estradiol benzoate (20 micrograms/day for 1 or 8 days). In female brains, 125I-SRIF binding, as assessed by film radioautography, was high in the basolateral amygdala, CA1 field and dentate gyrus of the hippocampus and locus coeruleus, moderate in the median habenula and deep layers all through the cortex. Castration or estradiol treatment did not modify 125I-SRIF binding in these regions. By light-microscopic radioautography, a subpopulation of 125I-SRIF-labeled cells was localized in the ventrolateral portion of the arcuate nucleus. Ovariectomy alone did not significantly affect the number and binding density of 125I-SRIF-labeled cells in the arcuate nucleus. However, estradiol treatment in ovariectomized animals significantly increased both parameters. Along the estrus cycle, the number of 125I-SRIF-labeled cells was not significantly modified but 125I-SRIF binding density was significantly higher in proestrus as compared to diestrus I, diestrus II and estrus. These results demonstrate that brain 125I-SRIF binding sites are positively regulated by estradiol only in the arcuate nucleus of the hypothalamus.
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PMID:Estradiol regulation of somatostatin receptors in the arcuate nucleus of the female rat. 135 70

Somatostatin and gamma-aminobutyric acid (GABA) are co-localized in some neurons in the CA1 area of the hippocampus. Since it is possible that the peptide and the amino acid are co-released, the interactions between the actions of somatostatin and GABA-ergic inhibitory post-synaptic potentials (IPSPs) in the CA1 pyramidal neurons of guinea pig hippocampal slices have been investigated. Somatostatin (2 microM) induced a hyperpolarization of the CA1 neurons associated with a reduction in the input resistance of the cells. These effects were not blocked by picrotoxinin (20 microM) or phaclofen (1 mM). Chelation of intracellular Ca2+ (Ca2+i) with BAPTA or the inhibition of protein kinase C (PKC) with sphingosine (30 microM) had no significant effects on the hyperpolarizing actions of somatostatin. The peptide suppressed the GABAA receptor-mediated fast IPSPs and the GABAB receptor-mediated slow IPSPs, but had no significant effect on the excitatory post-synaptic potentials (EPSPs). Somatostatin-induced depression of the IPSPs was not due to the hyperpolarization of the neurons. Baclofen (20 microM) suppressed the EPSP, as well as the fast and the slow IPSPs. The hyperpolarization of the CA1 neurons caused by somatostatin was greatly reduced in the presence of baclofen, an effect that was not due to the hyperpolarization of the cell by baclofen. The presence of QX-314 in the CA1 neurons, which suppressed the Na+ spikes and the slow IPSPs, prevented the hyperpolarization of the neurons by somatostatin and baclofen.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Actions of somatostatin on GABA-ergic synaptic transmission in the CA1 area of the hippocampus. 135 22

The influence of sustained epileptic seizures evoked by intraperitoneal injection of kainic acid on the gene expression of the neuropeptides somatostatin and neuropeptide Y and on the damage of neurons containing these peptides was studied in the rat brain. Injection of kainic acid induced an extensive loss of somatostatin and, though less pronounced, of neuropeptide Y neurons in the inner part of the hilus of the dentate gyrus. Neuropeptide Y-immunoreactive neurons located in the subgranular layer of the hilus, presumably pyramidal-shaped basket cells, were spared by the treatment. Although neuropeptide Y messenger RNA was not detected in granule cells of control rats, it was found there after kainic acid seizures at all time intervals investigated (12 h to 90 days after injection of kainic acid). High concentrations of neuropeptide Y messenger RNA were especially observed 24 h after injection of kainic acid. At this time neuropeptide Y messenger RNA was also transiently observed in CA1 pyramidal cells. Neuropeptide Y synthesis in granule cells in turn gave rise to an intense immunoreactivity of the peptide in the terminal field of mossy fibers which persisted for the entire time period (90 days) investigated. In addition, neuropeptide Y messenger RNA concentrations were also drastically elevated in presumptive basket cells located at the inner surface of the granule cell layer, especially at the "late" time intervals investigated (30-90 days after kainic acid). These data support the concept that extensive activation of granule cells by limbic seizures contributes to the observed neuronal cell death in CA3 pyramidal neurons and interneurons of the hilus. Consecutively, basket cells containing neuropeptide Y and presumably GABA might be activated and participate in recurrent inhibition of granule cells. Neuropeptide Y-immunoreactive fibers observed in the inner molecular layer at "late" time intervals after kainic acid may result either from collateral sprouting of mossy fibers or from basket cells extensively expressing the peptide. It is speculated that neuropeptide Y synthesized and released at a high rate from granule cells and basket cells may exert a protective action against seizures.
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PMID:Functional changes in neuropeptide Y- and somatostatin-containing neurons induced by limbic seizures in the rat. 136 Jan 55

Patient RB became amnesic following an episode of global ischemia that resulted in a bilateral lesion of the CA1 field of the hippocampus. This finding suggested that damage restricted to the hippocampus is sufficient to produce clinically significant memory impairment. To evaluate further the effect of ischemic brain damage on memory, we have developed an animal model of cerebral ischemia in the monkey. Monkeys were subjected to 15 min of reversible ischemia, using a noninvasive technique involving carotid occlusion and pharmacologically induced hypotension. These monkeys sustained significant loss of pyramidal cells in the CA1 and CA2 fields of the hippocampus, as well as loss of somatostatin-immunoreactive cells in the hilar region of the dentate gyrus. Cell loss occurred bilaterally throughout the rostrocaudal extent of the hippocampus but was greater in the caudal portion. Except for patchy loss of cerebellar Purkinje cells, significant damage was not detected in areas outside the hippocampus, including adjacent cortical regions, that is, entorhinal, perirhinal, and parahippocampal cortex, and other regions that have been implicated in memory function. On behavioral tests, the ischemic monkeys exhibited significant and enduring memory impairment. On the delayed nonmatching to sample task, the ischemic monkeys were as impaired as monkeys with lesions of the hippocampal formation and adjacent parahippocampal cortex (the H+ lesion). On two other memory tasks, the ischemic monkeys were less impaired than monkeys with the H+ lesion. In neuropathological evaluations, it has always been difficult to rule out the possibility that significant areas of neuronal dysfunction have gone undetected. The finding that ischemic lesions produced overall less memory impairment than H+ lesions indicates that the ischemic monkeys (and by extension, patient RB) are unlikely to have widespread neuronal dysfunction affecting memory that was undetected by histological examination. These results provide additional evidence that the hippocampus is a focal site of pathological change in cerebral ischemia, and that damage limited to the hippocampus is sufficient to impair memory.
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PMID:Enduring memory impairment in monkeys after ischemic damage to the hippocampus. 161 49

We investigated the relationship between somatostatin-like immunoreactivity (SSLI) and interictal spikes (IIS) in human temporal lobe epileptic tissue. IIS counted manually from depth electrode recordings obtained preoperatively were expressed as spike frequency in anterior, middle, and posterior portions of hippocampus. SSLI was determined by radioimmunoassay (RIA). An inverse relationship between SSLI in the entorhinal cortex (EC) and IIS frequency in hippocampus was present (r = -0.55, p = 0.06). No correlation between IIS and SSLI in CA4, CA3, CA1, or the dentate was evident. This finding suggests a role of the EC in generation, regulation, or expression of interictal paroxysmal electrical activity in temporal lobe epilepsy (TLE), for which somatostatin may be a marker.
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PMID:Interictal spikes and hippocampal somatostatin levels in temporal lobe epilepsy. 167 75

In the present work we characterized the kinetic properties of [125I]somatostatin pericellular binding sites in the arcuate nucleus of the hypothalamus of the rat by quantitative high-resolution light microscopic radioautography. In order to determine whether these pericellular binding sites corresponded to functional receptors, their properties were compared with those of previously well-characterized [125I]somatostatin binding sites present on neuronal processes on the same sections in the stratum radiatum of the CA1 of the hippocampus. Radiolabelled sections were analysed by densitometry using a Biocom image analysis system coupled with a Leitz orthoplan microscope. The linear relationship between optical densities and radioactive standards allowed us to quantitate [125I]somatostatin-specific binding. Binding was time- and temperature-dependent, and saturable and specific in the arcuate nucleus as in the CA1 of the hippocampus. Saturation experiments indicated a single receptor population of binding sites with KD values of 0.2 +/- 0.1 nM in the arcuate nucleus and 0.6 +/- 0.4 nM in the CA1. In both structures, displacement curves obtained with somatostatin 14 and somatostatin 28 were monophasic, but shallow, while the somatostatin analogue SMS 201-995 induced a biphasic displacement, suggesting two populations of binding sites. In both regions binding was GTP-dependent. Desaturation procedures (in vivo by cysteamine and in vitro by preincubating with GTP) resulted in an increase in the number of measurable binding sites.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Characterization of pericellular [125I]Tyr0 DTrp8 somatostatin binding sites in the rat arcuate nucleus by a newly developed method: quantitative high-resolution light microscopic radioautography. 167 3

Somatostatin receptor subtypes were labeled with the somatostatin analogs [125I]CGP 23996 and [125I]MK 678 and the distribution of these receptors in rat brain was investigated using quantitative autoradiographic techniques. [125I]CGP 23996 and [125I]MK 678 specifically label different populations of somatostatin receptors in rat brain. In a number of brain regions striking differences in the distribution of the somatostatin receptor subtypes labeled by each peptide were observed. High levels of binding sites for both [125I]CGP 23996 and [125I]MK 678 were present in the cerebral cortex, CA1 region and subiculum of the hippocampus. In contrast, high levels of [125I]MK 678 binding were found in the dentate gyrus of the hippocampus while few [125I]CGP 23996 binding sites were observed in this brain region. [125I]CGP 23996 binding was detected in the central region of the interpeduncular nucleus whereas the dorsal and lateral subnuclei of this brain area expressed mainly somatostatin receptors with high affinity for MK 678. The locus coeruleus and regions of the superior colliculus and hypothalamus selectively express [125I]MK 678-sensitive somatostatin receptors. Furthermore, limbic structures such as the lateral septum, the nucleus accumbens and ventromedial striatum had much higher levels of [125I]MK 678 binding sites than [125I]CGP 23996 binding sites. Differences in the expression of the somatostatin receptor subtypes were also detected in the substantia nigra. [125I]CGP 23996 binding was present in the pars reticulata but not the pars compacta whereas the reverse distribution for [125I]MK 678 binding sites was observed. The differential distribution of [125I]CGP 23996 and [125I]MK 678 binding sites in rat brain supports the hypothesis that these peptides selectively label different somatostatin receptor subtypes in the central nervous system.
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PMID:Differential distribution of somatostatin receptor subtypes in rat brain revealed by newly developed somatostatin analogs. 167 4


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