Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P61278 (somatostatin)
 22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Endocrine cells containing somatostatin (Som), gastrin-releasing peptide (GRP), and neuronal nitric oxide synthase (nNOS) and nerve fibers containing choline acetyl transferase (ChAT), tyrosine hydroxylase (TH), galanin (Gal), substance P (SP), and vasoactive intestinal polypeptide (VIP) were immunolocalized in the proventriculus of the Houbara bustard, Chlamydotis undulata. While GRP-immunoreactive (GRP-IR) cells occur in the inner zone, somatostatin (Som-IR) and polyclonal nNOS (nNOS-IR) immunoreactive cells were localized mainly in the peripheral zone of submucosal glands. GRP-IR, Som-IR, and nNOS-IR cells were occasionally observed in the walls of the gastric glands. Endocrine cells are of the closed variety and usually possess apical processes extending along the basal surfaces of adjacent nonreactive cells. Ultrastructural features of these cells are typical. ChAT, Gal, SP, VIP, and TH were immunolocalized in nerve fibers and terminals in the walls of arterioles and capillaries at the periphery of submucosal glands. Immunoreactivity to monoclonal nNOS occurred mainly in neuronal cell bodies in ganglia located around the submucosal glands. ChAT and TH immunoreactive cell bodies were also occasionally seen around the submucosal glands in the peripheral region. Immunoreactivity to Gal, SP, and VIP, but not ChAT or TH, was discernible around the walls of gastric glands. It was concluded that the distribution of neurotransmitters in neuronal structures is similar, but that of the endocrine cells varies from that of some avian species. The roles of these neurotransmitters in the regulation of acid secretion are discussed.
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PMID:Neurotransmitters regulating acid secretion in the proventriculus of the Houbara bustard (Chlamydotis undulata): a morphological viewpoint. 1130 48

Somatostatin receptor sst2 is an inhibitory G protein-coupled receptor, which inhibits normal and tumor cell growth by a mechanism involving the tyrosine phosphatase SHP-1. We reported previously that SHP-1 associates transiently with and is activated by sst2 and is a critical component for sst2 growth inhibitory signaling. Here, we demonstrate that in Chinese hamster ovary cells expressing sst2, SHP-1 is associated at the basal level with the neuronal nitric oxide synthase (nNOS). Following sst2 activation by the somatostatin analog RC-160, SHP-1 rapidly recruits nNOS tyrosine dephosphorylates and activates it. The resulting NO activates guanylate cyclase and inhibits cell proliferation. Coexpression of a catalytically inactive SHP-1 mutant with sst2 blocks RC-160-induced nNOS dephosphorylation and activation, as well as guanylate cyclase activation. In mouse pancreatic acini, RC-160 treatment reduces nNOS tyrosine phosphorylation accompanied by an increase of its activity. By opposition, in acini from viable motheaten (mev/mev) mice, which express a markedly inactive SHP-1, RC-160 has no effect on nNOS activity. Finally, expression of a dominant-negative form of nNOS prevents both RC-160-induced p27 up-regulation and cell proliferation inhibition. We therefore identified nNOS as a novel SHP-1 substrate critical for sst2-induced cell-growth arrest.
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PMID:Neuronal nitric oxide synthase: a substrate for SHP-1 involved in sst2 somatostatin receptor growth inhibitory signaling. 1151 20

Immunocytochemical techniques were used to examine the distribution of neurons immunoreactive (-ir) for nitric oxide synthase (nNOS), somatostatin (SOM), neuropeptide Y (NPY), parvalbumin (PV), calbindin (CB) and calretinin (CR), in the inferotemporal gyrus (Brodmann's area 21) of the human neocortex. Neurons that colocalized either nNOS or SOM with PV, CB or CR were also identified by double-labeling techniques. Furthermore, glutamate receptor subunit profiles (GluR1, GluR2/3, GluR2/4, GluR5/6/7 and NMDAR1) were also determined for these cells. The number and distribution of cells containing nNOS, SOM, NPY, PV, CB or CR differed for each antigen. In addition, distinct subpopulations of neurons displayed different degrees of colocalization of these antigens depending on which antigens were compared. Moreover, cells that contained nNOS, SOM, NPY, PV, CB or CR expressed different receptor subunit profiles. These results show that specific subpopulations of neurochemically identified nonpyramidal cells may be activated via different receptor subtypes. As these different subpopulations of cells project to specific regions of pyramidal cells, facilitation of subsets of these cells via different receptor subunits may activate different inhibitory circuits. Thus, various distinct, but overlapping, inhibitory circuits may act in concert in the modulation of normal cortical function, plasticity and disease.
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PMID:The human temporal cortex: characterization of neurons expressing nitric oxide synthase, neuropeptides and calcium-binding proteins, and their glutamate receptor subunit profiles. 1170 88

The neurochemical contents of hippocamposeptal projecting nonprincipal neurons were examined in the mouse brain by using retrograde labeling techniques. We used the immunofluorescent multiple labeling method with a confocal laser-scanning microscope. First of all, the hippocamposeptal projecting nonprincipal neurons were glutamic acid decarboxylase 67-immunoreactive (IR), i.e., these hippocamposeptal projecting nonprincipal neurons were immunocytochemically GABAergic in the mouse brain. Next, most (93.0%) of the hippocamposeptal projecting GABAergic neurons were somatostatin-like immunoreactive (SS-LIR). The SS-LIR hippocamposeptal projecting neurons were frequently found in the stratum oriens of the CA1 and CA3 regions, and were also occasionally found in the stratum radiatum, stratum lucidum, and stratum pyramidale of the CA3 region. They were also frequently found in the dentate hilus. On the other hand, at least 40.6% of SS-LIR neurons in the hippocampus projected to the medial septum. Next, 38.0% of hippocamposeptal projecting GABAergic neurons were calbindin D28K (CB)-IR. Although the distribution of the CB-IR hippocamposeptal projecting neurons was generally similar to that of the SS-LIR projecting neurons in Ammon's horn, they were never seen in the dentate hilus. At least 22.1% of CB-IR GABAergic neurons in the hippocampus projected to the medial septum. Furthermore, 5.8% of hippocamposeptal projecting GABAergic neurons were parvalbumin-IR, which were most always found in Ammon's horn. Finally, no hippocamposeptal projecting GABAergic neurons were neuronal nitric oxide synthase-IR nor calretinin-IR. These results indicate that the SS-LIR neurons play a crucial role in the hippocamposeptal projection of the mouse brain, and they are also assumed to be involved in the theta oscillation of the mouse hippocampus.
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PMID:Immunocytochemical characterization of hippocamposeptal projecting GABAergic nonprincipal neurons in the mouse brain: a retrograde labeling study. 1212 84

Nerve fibres play an important role in the regulation of gastric emptying. The aims of this study were to clarify the distribution, projections and origin of neuronal type nitric oxide synthase (NOS)-, tyrosine hydroxylase (TH)-, vesicular acetylcholine transporter (VAchT)- and peptide-containing nerve fibres of the rat pyloric sphincter. Extrinsic and local denervations of the sphincter were performed in order to reveal the origin and projections of the various nerve fibre populations. Pylorus from control and denervated animals were processed for the immunocytochemical demonstration of cholecystokinin (CCK), enkephalin, gastrin-releasing peptide (GRP), somatostatin, calcitonin gene-related peptide (CGRP), neuropeptide Y (NPY), pituitary adenylate cyclase-activating peptide (PACAP), substance P (SP), vasoactive intestinal peptide (VIP), galanin, NOS, VAchT and TH. VAchT, TH, nNOS, and all of the peptides investigated were found in nerve fibres innervating the pyloric sphincter, and coexistence of several putative neurotransmitters were revealed. Extrinsic denervation caused a total loss of NPY/TH-, SP/CGRP- and SP/CGRP/VIP/NOS/PACAP-containing nerve fibres. Local denervation immediately proximal to the sphincter markedly reduced the numbers of VIP/NOS/galanin- and VIP/NOS/galanin/PACAP +/- NPY-containing fibres within the sphincter suggesting an origin of these fibres in myenteric ganglia in the antral region; denervation at the level of the oxyntic-pyloric border had no effect. Local denervation immediately distal to the sphincter caused a marked decrease in VAchT-, SP/enkephalin-, enkephalin-, somatostatin-, CCK- and GRP-containing fibres within the sphincter suggesting that these emanate from the duodenum. The latter procedure also reduced the number of SP/CGRP-containing fibres of extrinsic origin within the pyloric sphincter.
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PMID:Origins and projections of nerve fibres in rat pyloric sphincter. 1213 47

The study was aimed at the immunohistochemical characterization of myenteric Stach type V neurons of the pig ileum that were not included in the widely used Dogiel classification. So far, this conspicuous population has been defined morphologically on the basis of silver-impregnated specimens only. By using neurofilament immunohistochemistry, type V neurons that occur singly or in aggregates could be identified unequivocally and could be distinguished from other smoothly contoured myenteric neurons, i.e., type II and type IV. Double-labeling immunohistochemistry revealed a number of potentially neuroactive substances or their synthesizing enzymes to be present in type V neurons. Choline acetyltransferase immunoreactivity (-ir) was found in all type V neurons, whereas neuronal nitric oxide synthase was detected in none. Leu-enkephalin-ir was found within 92.3%, somatostatin (SOM)-ir within 91.1%, calcitonin gene-related peptide (CGRP)-ir within 80.6% and met-enkephalin-ir within 74.7% of type V neurons. Triple-labeling immunohistochemistry was applied to address the question of a specific chemical coding for myenteric type V neurons. In contrast to other combinations of neuroactive substances/enzymes that were found in both type V and other, nontype V neurons, SOM/CGRP-ir was the only combination observed exclusively within type V neurons. Both substances were colocalized in 79.3% of type V neurons. This colocalization discriminates four-fifths of the type V neurons chemically from both type II neurons (CGRP positive, SOM negative) and type IV neurons (CGRP negative, SOM positive), which both share, at first glance, a similar morphology with type V neurons. These results further support the concept of a close correlation between morphologically defined neuronal type and chemical coding and, it is likely, also function in the enteric nervous system of larger mammals.
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PMID:Correlated morphological and chemical phenotyping in myenteric type V neurons of porcine ileum. 1235 27

Mechanical activation of the mucosal lining of the colon by brush stroking elicits an intestinal neural reflex and an increase in short circuit current (Isc) indicative of electrogenic chloride ion transport. We tested whether endogenous nucleotides are physiologic regulators of mucosal reflexes that control ion transport. The brush stroking-evoked Isc response in mucosa and submucosa preparations (M-SMP) of rat colon was reduced by the P2Y1 receptor (R) antagonist 2'deoxy-N6-methyl adenosine 3',5'-diphosphate diammonium salt (MRS 2179) and further blocked by tetrodotoxin (TTX). M-SMP Isc responses to serosal application of the P2Y1 R agonist 2-methylthioadenosine-diphosphate (2MeSADP) or the P2Y2/P2Y4 R agonist 5'uridine-triphosphate (UTP) were reduced but not abolished by TTX. The potency profile of nucleotides for increasing Isc was 5'adenosine-triphosphate (ATP; effective concentration at half maximal response [EC50] 0.65 x 10(4) M) congruent with UTP (EC50 1.0 x 10(-4) M) congruent with 2MeSADP (EC50 = 1.60 x 10(-4) M). Mucosal touch and distention-induced Ca2+ transients in submucous neurons were reduced by apyrase and prevented by blocking the P2Y1 R with MRS 2179 and TTX; denervation of the mucosa. It did not occur by touching a ganglion directly. 2MeSADP Ca2+ responses occurred in subsets of neurons with or without substance P (SP) responses. The potency profile of nucleotides on the neural Ca2+ response was 2MeSADP (5 x 10(-7) M) > UTP (6 x 10(-6) M) > ATP (9 x 10(-5) M). The expression of P2Y R immunoreactivity (ir) in nerve cell bodies was in the order of P2Y1 R > P2Y4 R >> P2Y2 R. P2Y1R ir occurred in the cell somas of more than 90% of neuronal nitric oxide synthase, vasoactive intestinal peptide (VIP), calretinin, or neuropeptide Y (NPY)-ir neurons, 78% of somatostatin neurons, but not in calbindin or SP neurons. P2Y2 R ir was expressed in a minority of SP, VIP, NPY, vesicular acetylcholine transporter, and calcitonin gene-related peptide-ir varicose fibers (5-20%) and those surrounding calbindin (5-20%) neurons. P2Y4 ir occurred mainly in the cell somas of 93% of NPY neurons. Reverse transcriptase polymerase chain reaction of the submucosa demonstrated mRNA for P2Y1R, P2Y2, P2Y4, P2Y6, and P2Y12 Rs. Expression of P2Y1, P2Y2, and P2Y4 protein was confirmed by western blots. In conclusion, endogenous nucleotides acting at P2YRs transduce mechanically evoked reflex chloride ion transport in rat distal colon. Nucleotides evoke reflexes by acting primarily at postsynaptic P2Y1 Rs and P2Y4 R on VIP+/NPY+ secretomotor neurons, at P2Y2 Rs on no more than 2% of VIP+ secretomotor neurons, and 2Y2 Rs mainly of extrinsic varicose fibers surrounding putative intrinsic primary afferent and secretomotor neurons. During mucosal mechanical reflexes, it is postulated that P2Y1 R, P2Y2 R, and P2Y4 R are activated by endogenous ATP, UTP, and 5'uridine-diphosphate.
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PMID:Mechanically evoked reflex electrogenic chloride secretion in rat distal colon is triggered by endogenous nucleotides acting at P2Y1, P2Y2, and P2Y4 receptors. 1468 71

In some brain regions, previous studies reported the frequent coexistence between neuronal nitric oxide synthase (nNOS) and somatostatin (SOM). In the hippocampus, nNOS and SOM were mainly expressed in GABAergic nonprincipal neurons. Here we estimated the immunocytochemical colocalization of nNOS and SOM in the mouse hippocampus using the optical disector. Both in the Ammon's horn and dentate gyrus, we encountered only a few nNOS-immunoreactive (IR)/SOM-like immunoreactive (LIR) neurons. They were mainly located in the stratum oriens of the Ammon's horn and in the dentate hilus. The nNOS-IR/SOM-LIR neurons usually showed characteristic large somata with thick dendrites, whereas the majority of nNOS-IR/SOM-negative neurons showed small somata with thin dendrites. Quantitative data revealed that the double-labeled cells represented only 4% and 7% of nNOS-IR neurons and SOM-LIR neurons, respectively, in the whole area of the hippocampus. We also found the laminar and dorsoventral differences in the degree of colocalization between nNOS and SOM. The percentages of nNOS-IR neurons containing SOM-like immunoreactivity were relatively high in the stratum oriens of the ventral CA1 region (24%), stratum lucidum of the dorsal CA3 region (29%) and dorsal dentate hilus (32%), but they were quite low in the other layers. On the other hand, the percentages of SOM-LIR neurons containing nNOS immunoreactivity were somewhat high in the stratum lucidum of the dorsal CA3 region (19%) and dorsal dentate hilus (28%), whereas they were very low in the other layers. Immunofluorescent triple labeling of axon terminals for nNOS, SOM and glutamic acid decarboxylase indicated that some nNOS-IR/SOM-LIR neurons might be dendritic inhibitory cells. The present results show the infrequent colocalization of nNOS and SOM in the mouse hippocampus, and also suggest that the double-labeled cells may be a particular subpopulation of hippocampal GABAergic nonprincipal neurons.
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PMID:Patterns of colocalization of neuronal nitric oxide synthase and somatostatin-like immunoreactivity in the mouse hippocampus: quantitative analysis with optical disector. 1502 20

The degeneration of selective and specific types of neurons is a characteristic feature in several neurodegenerative disorders. N-methyl-D-aspartate receptor (NMDAR) agonist quinolinic acid (QUIN)-induced excitotoxicity has been implicated in neurodegeneration and mimics Huntington's disease (HD) by the loss of medium-sized spiny projection neurons while sparing medium-sized aspiny interneurons in the striatum. Previous work suggests that somatostatin/neuropeptide Y (SST/NPY)-containing neurons are selectively preserved in HD due to the presence of nicotinamide adenine dinucleotide phosphate diaphorase (NADPH-d) and the lack of NMDAR. In the present study, the distribution of somatostatin (SST), neuropeptide Y (NPY), nitric oxide synthase (nNOS), NMDA receptor type-1 (NR1), and the enzyme NADPH-d was determined in cultured striatal neurons with the effect of QUIN and N-methyl-D-aspartate (NMDA). SST/NPY-positive neurons, which constitute approximately 8-10% of striatal neurons, are selectively spared in QUIN/NMDA-treated cultures. nNOS and NADPH-d-positive neurons, comprising 3.8% of the neuronal population, also exhibit selective resistance to excitotoxicity. Most NR1-positive neurons, which constitute >80% of the total neuronal population, are lost in majority upon treatment with QUIN and NMDA. SST and NADPH-d-positive neurons also colocalize with Cu/Zn superoxide dismutase (Cu/Zn SOD). In conclusion, our results thus demonstrate that SST/NPY/nNOS-positive neurons are selectively spared in NMDA agonist-induced excitotoxicity, which could be attributed to the presence of Cu/Zn SOD and NADPH-d in addition to the low abundance of NMDAR on these neurons.
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PMID:Characterization of striatal cultures with the effect of QUIN and NMDA. 1509 1

N-methyl-D-aspartate (NMDA) receptors are heteromeric assemblies of subunits (NR1 and NR2A-D), and are enriched in the striatum. Receptor phosphorylation has recently been demonstrated on the NR1 subunit at three serine residues, 897, 896, and 890, which appear to correspond to the level of receptor activity. In this study, expression of phospho-specific NR1 subunits at serine 897 (pNR1S897), serine 896 (pNR1S896), or serine 890 (pNR1S890) in neurochemically identified neurons of the adult rat striatum was detected by using double-immunofluorescent labeling or combined in situ hybridization and immunohistochemistry. In both the dorsal and ventral striatum, pNR1S897 was expressed at high levels in projection neurons containing >55% dynorphin (striatonigral) and >90% enkephalin (striatopallidal) and in interneurons that were 100% positive for choline, >90% positive for parvalbumin, and >45% positive for somatostatin (co-containing neuropeptide Y and neuronal nitric oxide synthase). Low levels of pNR1S896 were present in a small portion of projection neurons (<15% for both populations of projection neurons) and were almost lacking in the three types of interneurons. Interestingly, pNR1S890 was exclusively expressed in most parvalbumin-containing interneurons (70-80%). Acute administration of a psychostimulant, amphetamine, increased the number of dynorphin-containing projection neurons and parvalbumin interneurons showing detectable levels of pNR1S896 and pNR1S890, respectively. These results demonstrate the distinct expression of phospho-NR1 subunits in different populations of striatal projection neurons and interneurons at variable levels in normal rats; they also demonstrate that phosphorylation of NR1, at least on serine 896 and 890 sites, is sensitive to drug exposure.
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PMID:Distinct expression of phosphorylated N-methyl-D-aspartate receptor NR1 subunits by projection neurons and interneurons in the striatum of normal and amphetamine-treated rats. 1517 82


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