UNIPROT:P61278 - FACTA Search

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)

To estimate the functional role of endogenous somatostatin in the production of long-term potentiation (LTP) in mossy fiber-CA3 system, an influence of depletion of somatostatin on the magnitude of it was examined in guinea-pig hippocampal slices. Administration of cysteamine (200 mg/kg, s.c.), a depletor of somatostatin, to guinea-pigs 13 h prior to preparing slices resulted in a significant decrease in the magnitude of LTP of population spikes in mossy fiber-CA3 system, being associated with a significant depletion of the content of somatostatin in the hippocampus. Furthermore, bath-applied somatostatin (1-14) at a concentration, at which the substance did not influence LTP in slices prepared from saline-treated animals, significantly augmented LTP in slices from cysteamine-treated animals. Cyclo-somatostatin (0.32 and 3.2 microM), a putative antagonist of somatostatin receptors, failed to affect the magnitude of LTP of mossy fiber-CA3 system when applied alone; however, the combined application of cyclo-somatostatin with somatostatin (0.32 microM) significantly inhibited the augmenting action of somatostatin on LTP. From these observations, it is suggested that endogenous somatostatin plays a facilitatory role in the production of LTP in mossy fiber-CA3 system in guinea-pig hippocampus.
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PMID:A facilitatory role of endogenous somatostatin in long-term potentiation of the mossy fiber-CA3 system in guinea-pig hippocampus. 168 26

A detailed neurochemical analysis of the distribution of markers for the most relevant neurotransmitter systems within the rat hippocampal formation has been performed. The hippocampi, obtained from unfrozen brains of male Sprague-Dawley rats were subdissected into tissue parts containing mainly CA1, CA3 or the dentate gyrus, respectively. Each part was further divided into ventral and dorsal halves. In these six hippocampal subregions the concentrations of noradrenaline, dopamine, serotonin, 3-methoxy-4-hydroxyphenylglycol, 5-hydroxyindoleacetic acid and the putative neurotransmitter amino acids glutamate, aspartate, GABA, glycine and taurine, and the levels of somatostatin and neuropeptide Y and the activities of choline acetyltransferase, acetylcholinesterase and glutamate decarboxylase were measured. A marked heterogeneity in the subregional distribution of markers for various neurotransmitter systems within the hippocampal formation was observed. Each neuronal marker was characterized by an individual pattern of distribution. Most of the markers showed a concentration-gradient, increasing from dorsal to ventral; only taurine was more abundant in the dorsal than in the ventral parts and no dorsoventral difference was seen for aspartate, glycine and neuropeptide Y. The highest molar ratios of total 3-methoxy-4-hydroxyphenylglycol to noradrenaline and 5-hydroxyindoleacetic acid to serotonin were found in the dorsal hippocampus. The levels of noradrenaline, GABA and glutamate decarboxylase activity were highest in the dentate gyrus and lowest in CA1. The concentrations of somatostatin were highest in CA1; those of serotonin were highest in CA3. Highest activities of choline acetyltransferase and acetylcholinesterase were found in the dentate gyrus; lowest activities were found in CA3. In CA3 the lowest values of glutamate, aspartate, taurine and somatostatin were also found. The heterogeneity in the distribution of individual neurochemical markers allows insights into possible functional differences of hippocampal subregions and provides a relevant basis for future neurochemical investigations in this brain area.
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PMID:Regional heterogeneity in the distribution of neurotransmitter markers in the rat hippocampus. 168 35

The relationship between an episode of status epilepticus, the resulting hippocampal pathology, and the subsequent development of pathophysiological changes possibly relevant to human epilepsy was explored using the experimental epilepsy model of perforant path stimulation in the rat. Granule cell hyperexcitability and decreased feedforward and feedback inhibition were evident immediately after 24 hours of intermittent perforant path stimulation and persisted relatively unchanged for more than 1 year. All of the pathophysiological changes induced by perforant path stimulation were replicated in normal animals by a subconvulsive dose of bicuculline, suggesting that the permanent "epileptiform" abnormalities produced by sustained perforant path stimulation may be due to decreased GABA-mediated inhibition. Granule cell pathophysiology was seen only in animals that exhibited a loss of adjacent dentate hilar mossy cells and hilar somatostatin/neuropeptide Y-immunoreactive neurons. GABA-immunoreactive dentate basket cells survived despite the extensive loss of adjacent hilar neurons. However, parvalbumin immunoreactivity, present normally in a subpopulation of GABA-immunoreactive dentate basket cells, was absent on the stimulated side. Whether this represents decreased parvalbumin synthesis in surviving basket cells or a loss of a specific subset of inhibitory cells is unclear. Hyperexcitability and decreased paired-pulse inhibition in response to ipsilateral perforant path stimulation were also present in the CA1 pyramidal cell layer on the previously stimulated side, despite minimal damage to CA1 pyramidal cells or interneurons. The possibility that CA1 inhibitory neurons were hypofunctional or "dormant" due to a loss of excitatory input to inhibitory cells from damaged CA3 pyramidal cells was tested by stimulating the contralateral perforant path in order to activate the same CA1 basket cells via different inputs. Contralateral stimulation evoked CA1 pyramidal cell paired-pulse inhibition immediately in the previously stimulated hippocampus. Thus, we propose the "dormant basket cell" hypothesis, which implies that despite malfunction, inhibitory systems remain intact in "epileptic" tissue and are capable of functioning if appropriately activated.
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PMID:Permanently altered hippocampal structure, excitability, and inhibition after experimental status epilepticus in the rat: the "dormant basket cell" hypothesis and its possible relevance to temporal lobe epilepsy. 168 84

In CA3 hippocampal neurons of the rat, brief anoxic episodes produce a depolarization which is probably due to a synaptic release of glutamate. Diazoxide, an activator of ATP-sensitive K+ channels (K+ ATP), blocks the anoxic depolarization and has no effect in control oxygenated artificial cerebrospinal fluid. The hormone somatostatin which activates K+ ATP channels in the pancreas also reduces the anoxic depolarization in CA3 neurons. We suggest that drugs that open K+ ATP channels may constitute a novel approach to selectivity reducing the deleterious effects of excessive release of glutamate during anoxia without producing a generalized blockade of glutamatergic synaptic transmission.
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PMID:Activators of ATP-sensitive K+ channels reduce anoxic depolarization in CA3 hippocampal neurons. 197 42

The relationship between neuronal calcium binding protein content (calbindin D28K: CaBP and parvalbumin: PV) and vulnerability to ischemia was studied in different regions of the rat brain using the four vessel occlusion model of complete forebrain ischemia. The areas studied, i.e. the hippocampal formation, neocortex, neostriatum and reticular thalamic nucleus (RTN), show a characteristic pattern of CaBP and PV distribution, and are involved in ischemic damage to different degrees. In the hippocampal formation CaBP is present in dentate granule cells and in a subpopulation of the CA1 pyramidal cells, the latter being the most and the former the least vulnerable to ischemia. Non-pyramidal cells containing CaBP in these regions survive ischemia, whereas PV-containing non-pyramidal cells in the CA1 region are occasionally lost. Hilar somatostatin-containing cells and CA3 pyramidal cells contain neither PV nor CaBP. Nevertheless, the latter are resistant to ischemia and the former is the first population of cells that undergoes degeneration. Supragranular pyramidal neurons containing CaBP are the most vulnerable cell group in the sensory neocortex. In the RTN the degenerating neurons contain both PV and CaBP. In the neostriatum, ischemic damage involves both CaBP-positive and negative medium spiny neurons, although the degeneration always starts in the dorsolateral neostriatum containing relatively few CaBP-positive cells. The giant cholinergic interneurons of the striatum contain neither CaBP nor PV, and they are the most resistant cell type in this area. These examples suggest the lack of a consistent and systematic relationship between neuronal CaBP or PV content and ischemic vulnerability. It appears that some populations of cells containing CaBP or PV are more predisposed to ischemic cell death than neurons lacking these proteins. These neurons may express high levels of calcium binding proteins because their normal activity may involve a high rate of calcium uptake and/or intraneuronal release.
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PMID:Relationship of neuronal vulnerability and calcium binding protein immunoreactivity in ischemia. 207 50

The hippocampal pyramidal cells provide an example of how multiple potassium (K) currents co-exist and function in central mammalian neurones. The data come from CA1 and CA3 neurones in hippocampal slices, cell cultures and acutely dissociated cells from rats and guinea-pigs. Six voltage- or calcium(Ca)-dependent K currents have so far been described in CA1 pyramidal cells in slices. Four of them (IA, ID, IK, IM) are activated by depolarization alone; the two others (IC, IAHP) are activated by voltage-dependent influx of Ca ions (IC may be both Ca- and voltage-gated). In addition, a transient Ca-dependent K current (ICT) has been described in certain preparations, but it is not yet clear whether it is distinct from IC and IA. (1) IA activates fast (within 10 ms) and inactivates rapidly (time constant typically 15-50 ms) at potentials positive to -60 mV; it probably contributes to early spike-repolarization, it can delay the first spike for about 0.1 s, and may regulate repetitive firing. (2) ID activates within about 20 ms but inactivates slowly (seconds) below the spike threshold (-90 to -60 mV), causing a long delay (0.5-5 s) in the onset of firing. Due to its slow recovery from inactivation (seconds), separate depolarizing inputs can be "integrated". ID probably also participates in spike repolarization. (3) IK activates slowly (time constant, tau, 20-60 ms) in response to depolarizations positive to -40 mV and inactivates (tau about 5s) at -80 to -40 mV; it probably participates in spike repolarization. (4) IM activates slowly (tau about 50 ms) positive to -60 mV and does not inactivate; it tends to attenuate excitatory inputs, it reduces the firing rate during maintained depolarization (adaptation) and contributes to the medium after-hyperpolarization (mAHP); IM is suppressed by acetylcholine (via muscarinic receptors), but may be enhanced by somatostatin. (5) IC is activated by influx of Ca ions during the action potential and is thought to cause the final spike repolarization and the fast AHP (although ICT may be involved). Like IM, it also contributes to the medium AHP and early adaptation. It differs from IAHP by being sensitive to tetraethylammonium (TEA, 1 mM), but insensitive to noradrenaline and muscarine. Large-conductance (BK; about 200 pS) Ca-activated K channels, which may mediate IC, have been recorded. (6) IAHP is slowly activated by Ca-influx during action potentials, causing spike-frequency adaptation and the slow AHP. Thus, IAHP exerts a strong negative feedback control of discharge activity.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Potassium currents in hippocampal pyramidal cells. 220 97

Neuropeptide Y (NPY) immunoreactivity and gene expression was investigated in the hippocampus after kainic acid-induced seizures and pentylenetetrazol kindling in the rat. Pronounced increases of NPY immunoreactivity were found in the terminal field of mossy fibers in both animal models. In kainic acid-treated rats the peptide progressively accumulated in the hilus and the stratum lucidum of CA3, 5-60 days after injection of the toxin and, at the later intervals, extended to the supragranular molecular layer of the dentate gyrus indicating sprouting of these neurons. Unilateral injection of colchicine into the hilus abolished NPY staining of the mossy fibers. Using in situ hybridization, in both animal models markedly enhanced expression of prepro-NPY mRNA was observed in the granular layer, containing the perikarya of the mossy fibers. It is suggested that sustained expression of the neuromodulatory neuropeptide NPY, in addition to the observed plastic changes, may contribute to altered excitability of hippocampal mossy fibers in epilepsy. Neither somatostatin immunoreactivity nor gene expression were enhanced in granule cells/mossy fibers.
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PMID:Neuropeptide Y biosynthesis is markedly induced in mossy fibers during temporal lobe epilepsy of the rat. 235 14

Hippocampal CA3 neurons from fetal rats were grafted to excitotoxic lesions in the CA3 subfield of the adult rat hippocampus and the formation of graft-host brain nerve connections examined. The excitotoxic lesions were induced by localized, stereotaxic injection of ibotenic acid (IA), a glutamic acid agonist, into CA3 of the dorsal hippocampus. The result was a so-called axon-sparing lesion with localized degeneration of nerve cells, but preservation of the extrinsic afferent fibers, now deprived of their targets. One week after the lesion a suspension of embryonic (E18-20) CA3 cells was grafted to the lesion site. Six weeks or more later the recipient brains were processed and analyzed by ordinary cell stains, histochemistry for acetylcholinesterase (AChE) and heavy metals (Timm staining), immunohistochemistry for the neuropeptides cholecystokinin and somatostatin and glial fibrillary acidic protein (GFAP) for astroglia, electron microscopy, and axonal tracing with retrogradely axonal transported fluorescent dyes or lesion-induced, anterograde degeneration combined with silver staining or electron microscopy. More than 90% of the grafts survived. They contained the normal types of CA3 neurons, which are mainly pyramidal cells, in addition to some normal, peptidergic, cholecystokinin- and somatostatin-reactive neurons. The grafts were innervated by AChE-positive, host cholinergic fibers, Timm-positive mossy fiber terminals from the host fascia dentata, and host commissural fibers traced by axonal degeneration. Efferent transplant projections were traced to the ipsilateral host CA1 (Schaffer collaterals) and the contralateral host hippocampus by retrograde axonal transport of fluorochromes injected into these host brain areas. All grafts analyzed by electron microscopy contained axonal varicosities resembling axonal growth cones even after long survival times. The results demonstrate that fetal rat hippocampal neurons, grafted to excitotoxic, axon-sparing lesions in the adult brain, can become both structurally and connectively well incorporated in the mature host central nervous system.
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PMID:Grafting of fetal CA3 neurons to excitotoxic, axon-sparing lesions of the hippocampal CA3 area in adult rats. 239 68

Using the iodinated luteinizing-hormone-releasing hormone analogue [D-Ala6, N alpha MeLeu7, Pro9 NEt]-luteinizing-hormone-releasing hormone as radioligand, specific binding sites have been visualized in the rat both in the pituitary and the hippocampal formation of the brain. In the hippocampus, the CA1, CA2 and particularly CA3 regions were heavily labelled. These hippocampal sites have a pharmacological specificity resembling that of luteinizing-hormone-releasing hormone receptors in pituitary homogenates and could therefore represent true luteinizing-hormone-releasing hormone receptors. The luteinizing-hormone-releasing hormone superagonist [D-Ala6, Pro9 NEt]-luteinizing-hormone-releasing hormone and the potent antagonist [D-pGlu1, D-Phe2, D-Trp3,6]-luteinizing-hormone-releasing hormone were highly potent in displacing the iodinated luteinizing-hormone-releasing hormone analogue. The weak agonist [Gln8]-luteinizing-hormone-releasing hormone, however, was at least two orders of magnitude less potent. Somatostatin was inactive. Hippocampal luteinizing-hormone-releasing hormone receptors were species-specific, being present in the rat but not in the mouse, guinea-pig, hamster, rabbit and human brains. In order to identify the cellular location of these hippocampal receptors, various lesions were performed. Electrolytic lesions of the septal afferents did not reveal any receptor density change. Colchicine as well as kainic acid injections did, however, reduce considerably the number of hippocampal receptors. Interestingly, in the electrolytically and kainic-acid-lesioned animals, the appearance of non-displaceable luteinizing-hormone-releasing hormone binding sites within a well-defined area corresponding to the lesioned, gliosis-rich area was observed. The present results suggest the presence of pharmacologically specific, species-dependent, luteinizing-hormone-releasing hormone receptors located, at least partly, on intrinsic hippocampal neurons, in particular granule and pyramidal cells.
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PMID:Specific luteinizing-hormone-releasing hormone receptor binding sites in hippocampus and pituitary: an autoradiographical study. 281 69

The binding parameters and distribution of somatostatin receptors were determined in the rat brain using in vitro light microscopic autoradiography. The proteolysis resistant somatostatin analog (des-Ala1-, Gly2-desamino-Cys3Tyr11-dicarba3,14-somatostatin; CGP 23,996) radiolabeled with 125iodine proved to be suitable for the localization of somatostatin receptors. Slide mounted tissue sections showed that 125I-CGP 23,996 bound to the somatostatin receptor with a mean Kd value of 4.0 nM. The mean density of receptors (maximum binding) was determined to be 182 fmol/mg of protein. Both somatostatin and unlabeled CGP 23,996 displayed high-affinity binding for somatostatin receptors with IC50 values of 6 and 5 nM, respectively. The areas containing the highest densities of receptors are the basal amygdaloid nucleus, medial habenular nucleus, stratum oriens and radiatum of CA1 and CA2, and the subiculum. High receptor density can also be found in the deep layers of the cingulate cortex and in the deep layers of temporal cortex. Moderate densities occur in the caudate-putamen, the granule cell layer of the cerebellum, CA3 area of the hippocampus, the molecular layer of the dentate gyrus and in the substantia nigra. Brain areas with low specific binding include the molecular layer of the cerebellum and the corpus callosum, a white matter area.
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PMID:Light microscopic autoradiographic localization of somatostatin receptors in the rat brain. 286 34

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