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)

Somatostatin (SST) is one of the major peptide transmitters in the mammalian central nervous system and also seems to exert specific functions during brain development. In contrast to ligand binding experiments, by which two pharmacologically different binding sites were characterized, molecular cloning techniques have led to the identification of at least five different receptor subtypes (SSTR1-5), which according to RNA blot analyses seem to be differentially distributed and regulated in the developing brain. In order to provide more precise data on the distribution of SSTR1 during ontogenesis, we have performed an in situ hybridization analysis, using a 35S-labelled RNA probe, in the developing rat cortex between embryonic day (E)12 and adulthood. Within the cortical plate, expression of SSTR1 gene was first detected in parallel with the establishment of the deep laminae V/VI at E16, thereby following the characteristic morphogenetic gradients of cortical plate construction. Thus, with the subsequent addition of cells along the radial dimension, e.g. the deposition of the supragranular neurons beyond E18, the hybridization signal spreads as an uniform homogenous band through the entire cortical plate, whereby silver grains reach their peak density around birth. Similar developmental gradients were observed along the lateromedial and frontooccipital dimension, whereby SSTR1 transcripts were detected near the frontal pole and the lateral cortical areas roughly 2 days before they appeared in the occipital and medial cortical anlage, respectively. From the initially homogenous distribution, two distinct SSTR1 mRNA-positive bands coextensive with laminae V/VI and II/III, respectively, and sparing lamina IV evolved during the first postnatal week, the grain density of which decreased during further postnatal development. Within the hippocampal formation, SSTR1 transcripts were initially observed at E18 in the subicular complex, and after birth also extending into the neighboring CA1 region. During the 1st and 2nd postnatal week, silver grains were observed over the pyramidal cell layer of CA2 and CA3 and as a faint supragranular band in the dentate gyrus. Similar to the isocortex, grain density decreased thereafter. Hypothetically, the pronounced temporospatial regulation of SSTR1 gene expression during brain development can be correlated with (1) the establishment and eventual reduction of transient cortical SSTergic neuron populations described for late pregnancy and early postnatal development and (2) a receptor subtype exchange during maturation as evidenced by the late (from postnatal day 7 onward) appearance of e.g. SSTR3.
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PMID:Distribution of somatostatin receptor subtype 1 mRNA in the developing cerebral hemispheres of the rat. 857 44

Somatostatin-, neuropeptide Y-, neurokinin B- and cholecystokinin-containing neurons were investigated in the rat hippocampus in two chronic models of temporal lobe epilepsy, i.e. 30 days after rapid kindling or electrically induced status epilepticus (post-status epilepticus). After rapid kindling, somatostatin immunoreactivity was strongly increased in interneurons and in the outer and middle molecular layer of the dentate gyrus. In four of six post-status epilepticus rats (status epilepticus I rats), somatostatin immunoreactivity was slightly increased in the dorsal but decreased in the ventral dentate gyrus and molecular layer. Somatostatin immunoreactivity decreased in neurons of the dorsal hilus in the two other post-status epilepticus rats investigated, while a complete loss was found in the respective ventral extension (status epilepticus-II rats). These changes were associated with a different extent of neurodegeneration as assessed by Nissl staining. Similarly, neuropeptide Y immunoreactivity was enhanced in neurons of the hilus and in the middle and outer molecular layer of the dentate gyrus in the dorsal hippocampus of rapidly kindled and status epilepticus-I rats. Neuropeptide Y and neurokinin B immunoreactivity was enhanced in the mossy fibers of all post-status epilepticus rats, but not in the rapidly kindled rats. In status epilepticus-II rats, neuropeptide Y-and neurokinin B-positive fibers were also detected in the infrapyramidal region of the stratum oriens of CA3 and in the inner molecular layer of the dentate gyrus in the dorsal and ventral hippocampus respectively, labeling presumably sprouted mossy fibers. Increased staining of neuropeptide Y and neurokinin B was found in the alveus after rapid kindling. Cholecystokinin immunoreactivity was markedly increased in the cerebral cortex, Ammon's horn and the molecular layer of the dentate gyrus in the ventral hippocampus of rapidly kindled and post-status epilepticus rats. The lasting changes in the immunoreactive pattern of various peptides in the hippocampus may reflect functional modifications in the corresponding peptide-containing neurons. These changes may be involved in chronic epileptogenesis, which evolves in response to limbic seizures.
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PMID:Somatostatin, neuropeptide Y, neurokinin B and cholecystokinin immunoreactivity in two chronic models of temporal lobe epilepsy. 859 52

To characterize the nature and distribution of somatostatin (SRIF) receptors, radioligand binding studies and in vitro receptor autoradiography were performed in Rhesus monkey brain using either [125I]LTT-SRIF-28 ([Leu8, D-Trp22, 125I-Tyr25]SRIF-28) alone or in the presence of 3 nM seglitide (to block sst2 sites), [125I]Tyr3-octreotide or [125I]CGP 23996 (c[Asu-Lys-Asn-Phe-Trp-Lys-Thr-Tyr-Thr-Ser]) in buffer containing either 120 mM Na+ or 5 mM Mg2+. [125I]Tyr3 -octreotide labelled an apparently homogeneous population of sites in cerebral and cerebellar cortex (Bmax = 27.3 +/- 2.8 fmol/mg protein and 52.6 +/- 8.6 fmol/mg protein, PKd = 9.46 +/- 0.03 and] 9.93 +/- 0.03, respectively). The pharmacological profile of these sites correlated highly significantly with that of human recombinant sst2 receptors (r = 0.996), but not or much less with that of human recombinant sst3 and sst5 receptors (r = 0.12 and 0.45, respectively). [125I]CGP 23996 (in Na(+)-buffer) also labelled an apparently homogeneous population of sites in Rhesus monkey cerebral cortex membranes (Bmax = 3.1 +/- 0.3 fmol/mg protein, pKd = 10.57 +/- 0.08), the pharmacological profile of which was highly significantly correlated with the profiles of human recombinant sst1 and sst4 receptors (r = 0.98 and 0.96, respectively). Using receptor autoradiography, high levels of [125I]LTT-SRIF-28 and [125I]Tyr3 -octreotide recognition sites were found in basal ganglia, molecular and granular layers of the cerebellum and layers III, V and VI of entorhinal cortex. In these regions, the addition of 3 nM seglitide produced a marked decrease of [125I]LTT-SRIF-28 binding. Low levels of [125I]LTT-SRIF-28 binding were observed in subiculum, pituitary and choroid plexus. By contrast, [125I]CGP 23996 labelling in the presence of Mg2+ as well as Na+ ions was highest in pituitary and choroid plexus. However, [125I]CGP 23996 binding was diversely affected by these ionic conditions in several regions of hippocampus and cerebral cortex. Displacement of [125I]CGP 23996 (in Mg(2+)-buffer) with seglitide in the molecular layer of the cerebellum, deep layers of the entorhinal cortex, layers I, II and V of the insular cortex and frontal pole yielded complex competition curves suggesting the presence of two populations of SRIF receptors. By contrast, [125I]CGP 23996 binding (in Mg(2+)-buffer) in the choroid plexus, hilus of the dentate gyrus and stratum oriens and radiatum of the CA3 field of hippocampus was not affected by seglitide up to 10 microM, suggesting only sst1 and/or sst4 sites which have a negligible affinity for seglitide to be present in these structures. Taken together, these results suggest that [125I]CGP 23996 (in the presence of Na+) labels exclusively SRIF-2 receptors (sst1 and/or sst4), whereas in the presence of Mg2+ ions, [125I]CGP 23996 labels both SRIF-2 and SRIF-1 receptors (sst2, sst3 and sst5). The present study also demonstrates the presence and differential distribution of sst2 and sst1/sst4 receptors in the Rhesus monkey brain.
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PMID:Somatostatin receptors in the rhesus monkey brain: localization and pharmacological characterization. 873 98

Using immunocytochemistry and in situ hybridization analysis of mRNA, we investigated the changes in the expression of somatostatin and neuropeptide Y (NPY) in the rat hippocampal principal neurons in kindling or after electrically induced status epilepticus (SE), two models of limbic epilepsy associated with different chronic sequelae of seizures and seizure-related neuropathology. At the preconvulsive stage 2 of kindling and after three consecutive tonic-clonic seizures (stage 5) but not after a single-discharge (AD), somatostatin and NPY immunoreactivity (IR) were markedly increased in interneurons of the deep hilus and the polymorphic cell layer and their presumed projections to the outer molecular layer of the dentate gyrus. Increased mRNA levels were observed in the same neurons. NPY IR and mRNA were highly expressed in pyramidal-shaped basket cells at both stages of kindling. IR was similar two days after stages 2 or 5 of kindling while less pronounced effects were observed one week after kindling completion. Peptide-containing neurons in the hilus appeared well preserved in spite of an average of 24% reduction of Nissl stained cells (p < 0.01) in the stimulated and contralateral hippocampus at stage 5. No sprouting of mossy fibres in the inner molecular layer was found as assessed by Timm staining. Thirty days after SE, somatostatin IR was slightly reduced or similar to controls in the ventral dentate gyrus and molecular layer in four or six rats (SE-I group) while in the two other post-SE rats (SE-II), somatostatin IR was lost. These changes were associated with a different extent of neurodegeneration as assessed by cell counting of Nissl stained sections. In the granule cells/mossy fibres NPY-IR was transiently expressed at stage 2 and after a single AD. Differently, NPY-IR was persistently enhanced in the mossy fibres of all post-SE rats particularly in the SE-II group. In these rats, NPY immunoreactive fibres were detected in the infrapyramidal region of the stratum oriens CA3 and in the inner molecular layer of the dentate gyrus very likely labeling sprouted mossy fibres. In the hippocampus proper of kindled rats, somatostatin and NPY IR were respectively enhanced in the stratum lacunosum moleculare, the subiculum and in the alveus while no significant changes were observed after SE. Changes in peptide expression were bilateral and involved both the dorsal and the ventral hippocampus. The lasting modifications in peptides IR and mRNA expression in distinct neuronal populations of the hippocampus may reflect functional modifications neurons and play a role in limbic epileptogenesis.
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PMID:Functional changes in somatostatin and neuropeptide Y containing neurons in the rat hippocampus in chronic models of limbic seizures. 898 6

A specific antiserum against substance P receptor (SPR) labels nonprincipal neurons in the cerebral cortex of the rat (T. Kaneko et al. [1994], Neuroscience 60:199-211; Y. Nakaya et al. [1994], J. Comp. Neurol. 347:249-274). In the present study, we aimed to identify the types of SPR-immunoreactive neurons in the hippocampus according to their content of neurochemical markers, which label interneuron populations with distinct termination patterns. Markers for perisomatic inhibitory cells, parvalbumin and cholecystokinin (CCK), colocalized with SPR in pyramidallike basket cells in the dentate gyrus and in large multipolar or bitufted cells within all hippocampal subfields respectively. A dense meshwork of SPR-immunoreactive spiny dendrites in the hilus and stratum lucidum of the CA3 region belonged largely to inhibitory cells terminating in the distal dendritic region of granule cells, as indicated by the somatostatin and neuropeptide Y (NPY) content. In addition, SPR and NPY were colocalized in numerous multipolar interneurons with dendrites branching close to the soma. Twenty-five percent of the SPR-immunoreactive cells overlapped with calretinin-positive neurons in all hippocampal subfields, showing that interneurons specialized to contact other gamma-aminobutyric acid-ergic cells may also contain SPR. On the basis of the known termination pattern of the colocalized markers, we conclude that SPR-positive interneurons are functionally heterogeneous and participate in different inhibitory processes: (1) perisomatic inhibition of principal cells (CCK-containing cells, and parvalbumin-positive cells in the dentate gyrus), (2) feedback dendritic inhibition in the entorhinal termination zone (somatostatin and NPY-containing cells), and (3) innervation of other interneurons (calretinin-containing cells).
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PMID:Immunostaining for substance P receptor labels GABAergic cells with distinct termination patterns in the hippocampus. 903 94

We review our works on the pharmacological modulation of long-term potentiation (LTP) at guinea pig hippocampal mossy fiber-CA3 synapses in vitro. The magnitude of tetanus-induced LTP at the mossy fiber synapse was augmented by perfusion of slices with several cognitive enhancers, such as bifemelane (1 microM). The mossy fiber LTP was enhanced by somatostatin (0.32 microM) and inhibited in somatostatin-depleted slices from cysteamine-treated guinea pigs. An involvement of the 5-HT3 receptor also showed that granisetron (0.1 microM) enhanced the mossy fiber LTP. The above-mentioned enhancements by perfused agents were commonly reversed, at least in part, by muscarinic antagonists. However, the magnitude of mossy fiber LTP was bidirectionally modulated by muscarinic stimulations of slices with physostigmine or carbachol at different concentrations. The enhancing effects of high-concentration carbachol was antagonized by pirenzepine, and in contrast, the inhibition by low-concentration carbachol was antagonized in the presence of AF-DX116. When guinea pigs were preinjected with the cholinotoxin AF64A, the magnitude of LTP was decreased in the slices prepared from AF64A-treated animals. These results suggest that endogenous acetylcholine dominantly plays facilitatory roles through muscarinic M1 receptors in the induction of mossy fiber LTP. The pharmacological characterization of mossy fiber LTP may be of help to the evaluation of cognitive enhancers at a neuronal circuit level.
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PMID:Cognitive enhancers and hippocampal long-term potentiation in vitro. 906 59

The type 3 serotonin receptor (5-HT3R) is a ligand-gated ion channel whose presence in the CNS has been established by radioligand binding, in situ hybridization, and immunohistochemical analysis. To analyze further the role of the 5-HT3R in the CNS, we used in situ hybridization and immunocytochemistry to determine that 5-HT3R-expressing neurons are mainly GABA-containing cells in the rat telencephalon. We determined that 5-HT3R/GABA-containing neurons do not exhibit somatostatin immunoreactivity but often contain cholecystokinin (CCK) immunoreactivity. 5-HT3R-expressing cells with CCK immunoreactivity were observed in the neocortex, olfactory cortex, hippocampus, and amygdala. The 5-HT3R/CCK interneurons represent between 35 and 66% of the total population of CCK-containing cells in the neocortex. Further characterization of the 5-HT3R/GABAergic neurons was based on their calcium-binding protein immunoreactivity and showed that these neurons lack parvalbumin (PV) and represent a subpopulation of calbindin (CB)-containing interneurons that were preferentially present in the CA1-CA3 subfield of the hippocampus. Although some 5-HT3R/GABAergic neurons with calretinin (CR) were found in the neocortex, olfactory cortex, hippocampus, and amygdala, these neurons were more often present in the agranular insular and piriform cortices. We conclude that the neuronal expression of the 5-HT3R is selective within the GABA neuron population in the rat telencephalon. These 5-HT3R-expressing interneurons might contain CCK, CB, and CR. We suggest that serotonin through the 5-HT3R may regulate GABA and CCK neurotransmission in the telencephalon.
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PMID:The 5-HT3 receptor is present in different subpopulations of GABAergic neurons in the rat telencephalon. 909 50

In the present study we examined the distribution of chemically identified subpopulations of nonprincipal neurons in the rat hippocampus, focusing on the dorsoventral differences in their distributions. The subpopulations analyzed were those immunoreactive for parvalbumin, calretinin, nitric oxide synthase, somatostatin, calbindin D28K, vasoactive intestinal polypeptide and cholecystokinin. Using a confocal laser scanning light microscope, we could confirm that the penetration of each immunostaining, except that of calbindin D28K, was complete throughout 50 microns thick sections under our immunostaining conditions. We counted numbers of immunoreactive somata according to the 'dissector' principle, measured areas of hippocampal subdivisions and the thickness of sections, and estimated the approximate numerical densities of these subpopulations, especially for those neurons immunoreactive for nitric oxide synthase, calretinin, somatostatin and parvalbumin. Generally speaking, neurons immunoreactive for parvalbumin showed no significant dorsoventral differences in the numerical densities in any of the subdivisions of the hippocampus, whereas the numerical densities of somata immunoreactive for calretinin, nitric oxide synthase and somatostatin were significantly larger in ventral levels than at dorsal levels of the hippocampus. The numerical density of somatostatin neurons was significantly larger in ventral levels than in dorsal levels of the denate gyrus, and, although not prominent, of the CA1 region. That of nitric oxide synthase positive neurons was significantly larger in ventral levels than in dorsal levels of the CA3 region as well as of the DG but not of the CA1 region. The numerical density of calretinin positive neurons was larger in ventral levels than in dorsal levels of all hippocampal subdivisions. The present study also revealed that dorsal and ventral levels of the hippocampus differ from each other in the composition of their nonprincipal neurons.
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PMID:Distribution of nonprincipal neurons in the rat hippocampus, with special reference to their dorsoventral difference. 909 69

To study possible cellular targets and subcellular sites of action of opioid ligands in the rat hippocampus, we examined the distribution of the delta opioid receptor (DOR) by immunocytochemistry. By light microscopy, numerous interneurons, or non-principal cells, were intensely labeled for DOR, whereas the CA1 and CA3 pyramidal cells were lightly labeled. DOR-immunoreactive interneurons were found throughout the hippocampus but were particularly concentrated in stratum oriens of the CA1 region. Double labeling immunofluorescence revealed that DOR-immunoreactivity was found in a subpopulation of gamma-aminobutyric acid (GABA)-containing interneurons, which included most somatostatin-immunoreactive cells. Electron microscopic analysis of sections singly labeled for DOR revealed that DOR-immunoreactive profiles were abundant and widespread throughout all hippocampal lamina and had a similar distribution in CA1 and CA3. DOR-immunoreactivity was sometimes found in dendrites, which corresponded in morphology to those of interneurons. In addition, DOR-labeling was found in the shafts and spines of many dendrites, which exhibited the morphology of pyramidal cell dendrites. Within dendrites, dense DOR-immunoreactivity was associated with the plasmalemmal surface at or near the postsynaptic density, usually of asymmetric synapses. In addition, DOR labeling was present in a heterogeneous population of axon terminals, as well as in astrocytic profiles. At mossy fiber synapses, DOR labeling was occasionally found at both pre-and post-synaptic sites. These studies demonstrate that DOR is present at multiple sites on diverse cell types where it may function to regulate neuronal activity in the hippocampus.
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PMID:Localization of delta opioid receptor immunoreactivity in interneurons and pyramidal cells in the rat hippocampus. 913 74

In the present study we examined the laminar distributions of four types of chemically defined subpopulations of non-principal neurons, that is, those immunoreactive for parvalbumin (PV), calretinin (CR), nitric oxide synthase (NOS) and somatostatin (SS), in the rat hippocampus, by estimating their approximate numerical densities (NDs) and percentages in specific layers according to the 'disector' principle. CR-immunoreactive (CR-IR) neurons and NOS-IR neurons were scattered throughout layers, but among layers in each subdivision their NDs were largest in the principal cell layers, where 30-45% of CR-IR and NOS-IR somata in each subdivision were located. In addition, CR-IR and NOS-IR somata were also concentrated at the border between the stratum radiatum (SR) and stratum lacunosum moleculare (SLM) in the CA1 region, where the NDs of these neurons were far larger than those in the SR/SLM as a whole and close to those in the stratum pyramidale (SP) (CR-IR somata at the ventral level and NOS-IR somata at the dorsal level) or larger (NOS-IR neurons at the ventral level). The NDs of CR-IR somata were dorsoventrally different in all layers of the CA3 region, the SR/SLM in the CA1 region and the hilus and the granule cell layer (GCL) of the dentate gyrus (DG), whereas the NDs of NOS-IR somata were dorsoventrally different in all layers of the CA3 region and the SP in the CA1 region. In contrast, approx. 90% of somatostatin-like immunoreactive (SS-LIR) neurons were located in the stratum oriens/alveus (SO/SA) in the CA1 region and in the hilus of the DG, where they were the most predominant cell type among the four types of non-principal cells. In contrast, in the CA3 region, SS-LIR somata were scattered in various layers. The majority (50-70%) of PV-IR neurons were located in the principal cell layers, whereas one-fourth to one-third of them were located in the SO/SA and hilus. The NDs in the SP of the CA1 and CA3 regions showed a significant dorsoventral difference. Although PV-IR somata were most numerous among the four non-principal cell groups in the SP of the dorsal CA1 region, they were not necessarily predominant in the principal layers in other regions, that is, in the ventral CA1 region, CA3 region and DG, where the NDs of CR-IR and/or NOS-IR somata were nearly equal to or larger than that of PV-IR somata. The present study not only reveals the laminar distribution patterns of four types of non-principal neurons in each subdivision quantitatively, but also illustrates the prominent differences in the compositions of four types of non-principal cells in each layer of each subdivision.
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PMID:Laminar distribution of non-principal neurons in the rat hippocampus, with special reference to their compositional difference among layers. 929 10


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