UNIPROT:P61278 - FACTA Search

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Query: UNIPROT:P61278 (somatostatin)
22,083 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The thyrnus provides an optimal cellular and humoral microenvironment for the development of immunocompetent T lymphocytes. Although yolk sac derived pre-T, committed hematopoietic stem cells enter the thymus using a homing receptor, the immigration process also requires secretion of a peptide, called thymotaxin by the cells of the reticulo-epithelial (RE) network of the thymic cellular microenvironment. The thymic RE cells are functionally specialized based on their location within the thymic microenvironment. Thus, although subcapsular, cortical, and medullary RE cells are derived from a common, endodermal in origin epithelial precursor cell, their unique location within the gland causes their specialization in terms of their immunophenotypical and in situ physiological properties. The subcapsular, endocrine, RE cell layer (giant or nurse cells) is comprised of cells filled with PAS positive granules, which also express A2B5/TE4 cell surface antigens and MHC Class I (HLA A, B, C) molecules. In contrast to the medullary RE cells, these subcapsular nurse cells also produce thymosins beta 3 and beta 4. The thymic nurse cells (TNCs) display a neuroendocrine cell specific immunophenotype (IP): Thy-1+, A2B5+, TT+, TE4+, UJ13/A+, UJ127.11+, UJ167.11+, UJ181.4+, and presence of common leukocyte antigen (CLA+). Medullar RE cells display MHC Class II (HLA-DP, HLA-DQ, HLA- DR) molecule restriction. These cells also contain transforming growth factor (TGF)-beta type II receptors and are involved in the positive selection of T cells. Transmission electronmicroscopic (TEM) observations have defined four, functional subtypes of medullary RE cells: undifferentiated squamous, villous and cystic. All subtypes were connected with desmosomes. The secreted thy nic hormones, thymulin, thymosin-alpha 1 and thymopoietin (its short form, thymopentin or TP5) were detected immunocytochemically to be produced by RE cells. Thymic RE cells also produce numerous cytokines including IL-1, IL-6, G-CSF, M-CSF, and GM-CSF molecules that likely are important in various stages of thymocyte activation and differentiation. The co-existence of pituitary hormone and neuropeptide secretion [growth hormone (GH), prolactin (PRL), adrenocorticotropic hormone (ACTH), thyroid stimulating hormone (TSH), triiodothyronine (T3), somatostatin, oxytocin (OT), follicle stimulating hormone (FSH), luteinizing hormone (LH), arginine vasopressin (AVP), growth hormone releasing hormone (GHRH), corticotropin releasing hormone (CRH), nerve growth factor (NGF), vasoactive intestinal peptide (VIP), pro-enkephalin (pro-enk), and beta-endorphin (beta-end)], as well as production of a number of interleukins and growth factors and expression of receptors for all, by RE cells is an unique molecular biological phenomenon. The thymic RE cell network is most probably comprised of cells organized into sub-networks--functional units composed of RE cells with differing hormone production/hormone receptor expression profiles, involved in the various stages of T lymphocyte maturation. Furthermore, it is quite possible that even on the level of individual RE cells, the numerous projections associated with a single cell, which engulf developing lymphocytes, nurturing and guiding them in their maturation, may differ in their hormone production and/or hormone receptor expression profile, thus allowing a single cell to be involved in distinct, separate steps of the T cell maturation process. Based on our systematic observations of the thymus in humans and other mammalian species, we suggest that the thymic RE cells represent an extremely important cellular and humoral network within the thymic microenvironment and are involved in the homeopathic regulation mechanisms of the multicellular organism, in addition to the presentation of various antigens to developing lymphocytes, and providing growth regulatory signals which may range from stimulatory to apoptotic signaling within the thymus. (ABSTRACT TRUNCA
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PMID:The role of the reticulo-epithelial (RE) cell network in the immuno-neuroendocrine regulation of intrathymic lymphopoiesis. 1092 21

Although the long-lasting effects of neurotrophins have been extensively studied, less data are available on their rapid effects, especially on peptide release. In the present report, we investigated rapid effects of neurotrophins on somatostatin release and on intracellular calcium concentration ([Ca(2+)](i)) in primary cultures of hypothalamic neurons. RT-PCR experiments revealed mRNA expression of the three high-affinity neurotrophin receptors tyrosine kinase (Trk) TrkA, TrkB and TrkC, indicating potential responses to their preferential ligands: nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF) and neurotrophin 3 (NT-3), respectively. We demonstrated that BDNF, and to a lesser extent NT-3, induced significant time- and concentration-dependent somatostatin release, while NGF was devoid of any effect. BDNF or NT-3 induction of somatostatin release was inhibited by the Trk inhibitors K-252a and genistein, whereas K-252b, a less effective inhibitor, had no effect. BDNF- and NT-3-induced somatostatin release depended upon extra- and intracellular Ca(2+) since it was completely abolished in the presence of the Ca(2+) chelators BAPTA (bis-(alpha-aminophenoxy)-ethane-N,N,N',N'-tetraacetic acid) or BAPTA-AM (bis-(alpha-aminophenoxy)-ethane-N,N,N',N'-tetraacetoxymethylester), respectively. In addition, BDNF and NT-3 induced a sustained and rapid increase in [Ca(2+)](i) which depended on the extracellular Ca(2+) concentration. MK-801 (dizocilpine) and tetrodotoxin (TTX) entirely blocked neurotrophin-evoked somatostatin release and [Ca(2+)](i) rise in response to BDNF and NT-3 application in most neurons. Neurotrophin-induced [Ca(2+)](i) rise was completely blocked by K-252a. The present results are consistent with: (1) an indirect effect of neurotrophins on somatostatin release via endogenous glutamate release and subsequent NMDA receptor activation, (2) a major indirect effect of neurotrophins on Ca(2+) rise in hypothalamic neurons which very likely occurs through NMDA receptor activation. Taken altogether, these results indicate that BDNF and NT-3 can rapidly affect the activity of hypothalamic neurons.
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PMID:Rapid stimulatory effects of brain-derived neurotrophic factor and neurotrophin-3 on somatostatin release and intracellular calcium rise in primary hypothalamic cell cultures. 1143 57

The neurons labeled by isolectin B4 (IB4) in rat and mouse sensory ganglia are often regarded as non-nerve growth factor (NGF)-dependent and non-peptidergic neurons, but a considerable number of IB4-positive neurons in the dorsal root ganglion (DRG) are also shown to be immunoreactive to substance P (SP) and calcitonin gene-related peptide (CGRP), which are synthesized by NGF-dependent neurons. Therefore, we examined the relationships between the IB4-binding neurons and NGF/glial cell line-derived neurotrophic factor (GDNF)/GDNF-related proteins(GDNFs)-dependent neurons in rat DRGs by use of in situ hybridization histochemistry in serial sections. Of the DRG neurons, 42% and 22% were intensely and weakly labeled by IB4, respectively. The former neurons were small, and the latter varied in size. Of the trkA mRNA-expressing neurons, 29% and 57% were intensely and weakly labeled by IB4, respectively. On the other hand, 66% and 10% of the c-ret mRNA-expressing neurons were intensely and weakly labeled, respectively. The mRNA of somatostatin, another major neuropeptide in the sensory neurons, was exclusively expressed in the intensely IB4-labeled neurons. These findings suggest that many NGF-dependent and peptidergic sensory neurons are labeled by IB4 in rats.
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PMID:Difference in binding by isolectin B4 to trkA and c-ret mRNA-expressing neurons in rat sensory ganglia. 1168 73

Transcriptional profiling (TP) offers a powerful approach to identify genes activated during memory formation and, by inference, the molecular pathways involved. Trace eyeblink conditioning is well suited for the study of regional gene expression because it requires the hippocampus, whereas the highly parallel task, delay conditioning, does not. First, we determined when gene expression was most regulated during trace conditioning. Rats were exposed to 200 trials per day of paired and unpaired stimuli each day for 4 days. Changes in gene expression were most apparent 24 h after exposure to 200 trials. Therefore, we profiled gene expression in the hippocampus 24 h after 200 trials of trace eyeblink conditioning, on multiple arrays using additional animals. Of 1,186 genes on the filter array, seven genes met the statistical criteria and were also validated by real-time polymerase chain reaction. These genes were growth hormone (GH), c-kit receptor tyrosine kinase (c-kit), glutamate receptor, metabotropic 5 (mGluR5), nerve growth factor-beta (NGF-beta), Jun oncogene (c-Jun), transmembrane receptor Unc5H1 (UNC5H1), and transmembrane receptor Unc5H2 (UNC5H2). All these genes, except for GH, were downregulated in response to trace conditioning. GH was upregulated; therefore, we also validated the downregulation of the GH inhibitor, somatostatin (SST), even though it just failed to meet criteria on the arrays. By during situ hybridization, GH was expressed throughout the cell layers of the hippocampus in response to trace conditioning. None of the genes regulated in trace eyeblink conditioning were similarly affected by delay conditioning, a task that does not require the hippocampus. These findings demonstrate that transcriptional profiling can exhibit a repertoire of genes sensitive to the formation of hippocampal-dependent associative memories.
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PMID:Transcriptional profiling reveals regulated genes in the hippocampus during memory formation. 1254 33

(1) Peripheral inflammation causes an increase in the proportion of primary afferent neurones that express neurokinin(1) (NK(1)) receptors for substance P (SP). This upregulation may contribute to the neuronal mechanisms of inflammatory pain. The aim of this study was to identify endogenous mediators that stimulate upregulation of NK(1) receptors in dorsal root ganglion (DRG) neurones. Cultured DRG neurones from the adult normal rat were exposed for 2 days to media that contained specific mediators, namely potassium in high concentration, prostaglandin E(2) (PGE(2)), somatostatin (SRIF), and compounds influencing second messenger cascades. After fixation neurones were labelled with an NK(1) receptor antibody. (2) Repetitive addition of the inflammatory mediator PGE(2) or dibutyryl-cyclic adenosine 3',5' monophophate (db-cAMP) to the culture medium enhanced the proportion of neurones with NK(1) receptor-like immunoreactivity from about 12% up to 40%. PGE(2)-induced upregulation was prevented by coadministration of PGE(2) and a protein kinase A inhibitor or SRIF to the medium. High potassium concentration, protein kinase C inhibitors and omission of nerve growth factor from the medium had no effect. (3) In calcium-imaging experiments, bath application of SP evoked increases of the intracellular calcium concentration in about 20% of the neurones. This proportion increased to about 40% after PGE(2)-pretreatment, but the increase was prevented when PGE(2) and SRIF were coadministered to the medium. (4) These data show that the expression of NK(1) receptor-like immunoreactivity in DRG neurones is regulated by the inflammatory mediator PGE(2). This upregulation depends on the intracellular adenylyl cyclase-protein kinase A pathway.
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PMID:Prostaglandin E2 increases the expression of the neurokinin1 receptor in adult sensory neurones in culture: a novel role of prostaglandins. 1278 27

Neurotomy is widely used as a model of chronic, intractable pain, the proverbial "crux medicorum". Immunohistochemical aspects of this chronic pain model are discussed in this paper, with the aim of shedding new light on the pathomechanism and possible therapeutical consequences. Central terminals of nociceptive neurons contain substance P, somatostatin and calcitonin generelated peptide or exhibit fluoride resistant acid phosphatase and thiamine monophosphatase enzyme reaction in the superficial dorsal horn of the spinal cord and in analogous structures of the brain stem. These neuropeptides and neuroproteins are expressed by the related dorsal root ganglion cells and transported via orthograde axoplasmic transport via dorsal roots to the central nervous system. Transection of the ipsilateral, segmentally related peripheral sensory nerve results in transganglionic degenerative atrophy of central terminals of primary nociceptive neurons. Transganglionic degenerative atrophy is characterized by marked ultrastructural alterations superficially similar to, but essentially differing from the signs of Wallerian degeneration which ensue after dorsal rhizotomy. Transganglionic degenerative atrophy is accompanied by depletion of marker neuropeptides and enzymes, and later by the expression of vicarious neuropeptides such as vasoactive intestinal polypeptide, neuropeptide Y and galanin and of the enzyme choline acetyl transferase. Consequences of blockade of retrograde axoplasmic transport of the nerve growth factor elicited either by perineural application of microtubule inhibitors or by perineural administration of anti-nerve growth factor are similar to peripheral neurotomy. According to recent studies described in this paper, the blockade of nerve growth factor supply to primary nociceptive neurons induces activation of c-jun in nuclei of primary nociceptive neurons probably responsible for the plasticity of the neuropeptide and neuroprotein synthesizing machinery. In contrast, invasion of and formation of pericellular baskets by noradrenergic axons can be elicited only by axotomy and not by blockade of retrograde axoplasmic transport. Involvement of nerve growth factor and the nerve growth factor-dependent immediate early genes in neuroplasticity of neuropeptidergic primary sensory neurons raise the possibility of a gene therapy of chronic intractable pain.
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PMID:Molecular plasticity of primary nociceptive neurons: relations of the NGF-c-jun system to neurotomy and chronic pain. 1292 68

Several neuropeptides affect the sleep-wake cycle, for example, vasoactive intestinal polypeptide, cholecystokinin octapeptide, orexin, somatostatin, insulin, leptin, ghrelin, neuropeptide Y and cortistatin, which regulate food ingestion. There are also proteins from the immunological system: tumor necrosis factor-alpha, interleukin (IL)-1beta IL-4, IL-10, IL-13, as well as trophic molecules, such as growth hormone-releasing hormone, growth hormone, prolactin, brain-derived neurotrophic factor and nerve growth factor, neurotrophin-3 and neurotrophin-4. Based on this information, we believe that some functions of sleep can be suggested. One of these functions could be the regulation of energy, since many, if not all, of the neuropeptides that regulate feeding affect the level of alertness. Likewise, the immunological system and the trophic molecules establish a dialog with the brain during sleep in order to reestablish neuronal structure. These proteins are the expression of genes that accomplish the function of regulating our waking and our sleep, suggesting the important control the genome is exerting on this activity.
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PMID:The role of neuropeptides in sleep modulation. 1560 11

Tissue destruction is accompanied by an inflammatory reaction. The inflammatory reaction leads to activation of nociceptors and the sensation of pain. Several mediators are responsible for pain and hyperalgesia in inflammation including cytokines, chemokines, nerve growth factor as well as bradykinin, prostaglandins and ATP. Simulatenously however, analgesic mediators are secreted: opioid peptides, somatostatin, endocannabinoids and certain cytokines. Opioid peptides secreted from immune cells are so far the best studied peptides in peripheral inflammatory pain control. This system is hampered for example by anti-adhesion molecule treatment. Novel immunosuppressive drugs for treatment of autoimmune disease targetting cytokines, chemokines or adhesion molecules should therefore be evaluated for potential harmful effects on pain.
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PMID:Involvement of cytokines, chemokines and adhesion molecules in opioid analgesia. 1573 96

The effects of brain-derived neurotrophic factor (BDNF) on the development of presynaptic terminals and of neuronal subtypes in various brain areas were studied in BDNF-knockout (BDNF-/-) mice at postnatal days 15-17. Western analysis revealed no changes in the overall amount of a variety of synaptic proteins in BDNF-/- mice as compared to wild type mice. In addition, the complex between the vesicular proteins, synaptophysin and synaptobrevin, as well as their respective homodimers were unaltered. Moreover, no changes in the density of neurons were found in, e.g., the CA3 region of the hippocampus and the nucleus nervi facialis of BDNF-/- mice. However, cholinergic cells were reduced by 20% in the medial septum of BDNF-/- mice associated with a decrease in the activity of choline acetyltransferase and protein levels of nerve growth factor in the hippocampus by 16% and 44%, respectively. In the striatum, however, the total number of cholinergic cells were comparable in both groups, although the activity of choline acetyltransferase was decreased by 46%. In GABAergic interneurons, the expression of neuropeptides in various brain areas was differentially affected by BDNF deletion as revealed by immunohistochemistry. In the hippocampus and cortex of BDNF-/- mice, the density of neuropeptide Y-, somatostatin-, and parvalbumin-immunoreactive cells was drastically reduced, whereas the density of calretinin-positive cells was increased. The extent of these changes in neuropeptide-containing cells varied among hippocampal subregions. In the striatum, only the density of parvalbumin-immunoreactive cells was decreased by approximately 45%. In conclusion, BDNF deficiency is accompanied by a differential dysregulation in the expression of neuropeptides and calcium-binding proteins in otherwise intact GABAergic and glutamatergic neurons in a region-specific manner.
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PMID:Area-specific effects of brain-derived neurotrophic factor (BDNF) genetic ablation on various neuronal subtypes of the mouse brain. 1609 99

In the present study, we conducted: (i) in situ hybridization in order to investigate the expression of kainate and GABA(A) receptor subunits and the pre-proenkephalin and prodynorphin peptides in the brain of weaver mouse (a genetic model of dopamine deficiency) and (ii) immunocytochemistry in order to study the somatostatin-positive cells in weaver striatum. Our results indicated: (i) increases in mRNA levels of KA2 and GluR6 kainate receptor subunits, of alpha(4) and beta(3) GABA(A) receptor subunits and of pre-proenkephalin and prodynorphin in 6-month-old weaver striatum; (ii) a decrease in alpha(1) and beta(2) GABA(A) subunit mRNAs in 6-month-old weaver globus pallidus; (iii) increases in KA2, alpha(4) and beta(3) and decreases in alpha(2) and beta(2) mRNAs in the 6-month-old weaver somatosensory cortex; and (iv) an increase in somatostatin-immunopositive cells in 3-month-old weaver striatum. We suggest that: (i) in striatum, the alterations are induced by the induction of the transcription factor DeltafosB (for GluR6, pre-proenkephalin and prodynorphin mRNAs) and the suppression of transcription factors like NGF-IB (nerve growth factor inducible B; for the KA2 mRNA), in response to dopamine depletion; (ii) in striatum and cortex, the alterations in the expression of the GABA(A) subunits indicate an increase of extrasynaptic versus a decrease of synaptic GABA(A) receptors; and (iii) in globus pallidus, the increased striatopallidal GABAergic transmission leads to a decrease in the number of GABA(A) receptors. Our results further clarify the regulatory role of dopamine in the expression of amino acid receptors and striatal neuropeptides.
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PMID:Expression of amino acid receptors and neural peptides in the weaver mouse brain. 1662 33

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