Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

We examined the effects of ciliary neurotrophic factor (CNTF) and depolarization, two environmental signals that influence noradrenergic and cholinergic function, on neuropeptide expression by cultured sympathetic neurons. Sciatic nerve extract, a rich source of CNTF, increased levels of vasoactive intestinal peptide (VIP), substance P, and somatostatin severalfold while significantly reducing levels of neuropeptide Y (NPY). No change was observed in the levels of leu-enkephalin (L-Enk). These effects were abolished by immunoprecipitation of CNTF-like molecules from the extract with an antiserum raised against recombinant CNTF, and recombinant CNTF caused changes in neuropeptide levels similar to those of sciatic nerve extract. Alterations in neuropeptide levels by CNTF were dose-dependent, with maximal induction at concentrations of 5-25 ng/ml. Peptide levels were altered after only 3 days of CNTF exposure and continued to change for 14 days. Depolarization of sympathetic neuron cultures with elevated potassium elicited a different spectrum of effects; it increased VIP and NPY content but did not alter substance P, somatostatin, or L-Enk. Depolarization is known to block cholinergic induction in response to heart cell conditioned medium and we found that it blocked the induction of choline acetyltransferase (ChAT) and peptides by recombinant cholinergic differentiation factor/leukemia inhibitory factor (CDF/LIF). In contrast, it did not antagonize the effects of CNTF on either ChAT activity or neuropeptide expression. Thus, while CNTF has effects on neurotransmitter properties similar to those previously reported for CDF/LIF, the actions of these two factors are differentially modulated by depolarization, suggesting that the mechanisms of cholinergic and neuropeptide induction for the two factors differ. In addition, in contrast to CDF/LIF, CNTF did not alter levels of ChAT, VIP, substance P, or somatostatin in cultured dorsal root ganglion neurons. These observations indicate that CNTF and depolarization affect the expression of neuropeptides by sympathetic neurons and provide evidence for an overlapping yet distinct spectrum of actions of the two neuronal differentiation factors, CNTF and CDF/LIF.
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PMID:Effects of ciliary neurotrophic factor (CNTF) and depolarization on neuropeptide expression in cultured sympathetic neurons. 137 70

Chromaffin granules, the secretory organelles of the neuron-like adrenal medullary chromaffin cells, have previously been shown to store and liberate neurotrophic activities that support in vitro survival of several neuron populations including those innervating the adrenal medulla. Molecules resembling fibroblast growth factor and ciliary neurotrophic factor have been identified among these activities. Since chromaffin granules store a variety of neuropeptides and many neuropeptides can have pleiotropic effects on neuronal growth and maintenance we have tested 24 different neuropeptides for their capacities to promote survival of embryonic chick ciliary, dorsal root and sympathetic ganglionic neurons. Peptides tested included several derivatives of proenkephalin (Leu- and met-enkephalin, fragments BAM 22, B, F and E), somatostatin, substance P, neuropeptide Y, neurotensin, VIP, bombesin, secretin, pancreastatin, dynorphin B, dynorphin 1-13, beta-endorphin, alpha-, beta-, and gamma-MSH. Control cultures received saturating concentrations of ciliary neurotrophic or nerve growth factor (CNTF; NGF), or no trophic supplements. At 1 x 10(-5) M leu- and met-enkephalin as well as somatostatin supported sympathetic neurons to the same extent as NGF. At the same concentrations, leu-enkephalin, the proenkephalin fragments BAM 22 and E, and somatostatin maintained about half of the dorsal root ganglionic neurons supported by NGF, but were not effective on ciliary neurons. VIP promoted the survival of approximately 50% of the ciliary and embryonic day 10 dorsal root ganglionic neurons as compared to saturating amounts of CNTF, but required the presence of non-neuronal cells in the cultures to be effective. Neurotensin (1 x 10(-5) M had a small effect on ciliary neurons.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Screening of adrenal medullary neuropeptides for putative neurotrophic effects. 163 76

Effects of immune cytokines on neuronal gene expression have recently been examined in cultured superior cervical (sympathetic) ganglia, a widely used model system for the study of neurotransmitter plasticity. Following deafferentation and explantation into culture, interleukin-1 causes an up-regulation of the neuropeptide substance P as well as of choline acetyltransferase. Tumor necrosis factor-alpha has a similar, though less potent, action. Since interleukin-1 was ineffective in raising the concentration of substance P in pure neuronal cultures, the existence of a non-neuronally derived intermediate was postulated and found to exist in interleukin-1-conditioned medium. Antibody neutralization of either nerve growth factor or ciliary neurotrophic factor failed to affect the ability of interleukin-1 to induce substance P. Inhibition of prostaglandin biosynthesis was equally ineffective. However, immunoprecipitation of leukemia inhibitory factor from interleukin-1-conditioned medium eliminated substance-P-inducing activity, suggesting leukemia inhibitory factor as a possible interleukin-1-induced intermediate. The ability of interleukin-1 to induce leukemia inhibitory factor mRNA strengthens this conclusion. Glucocorticoid hormones block the interleukin-1 induction of leukemia inhibitory factor, which explains why they block the interleukin-1 induction of substance P.
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PMID:Neural-immune interactions in sympathetic ganglia. 752 15

Adult rat dorsal root ganglion sensory neurons in culture require nerve growth factor for synthesis of substance P and calcitonin gene-related peptide but express vasoactive intestinal peptide independently of nerve growth factor. In contrast, the same neurons from newborn rats do not express detectable vasoactive intestinal polypeptide when cultured with nerve growth factor. To further explore the mechanisms regulating neuropeptide expression in these cells, I compared the effects of nerve growth factor, brain-derived neurotrophic factor, neurotrophin-3, ciliary neurotrophic factor and leukaemia inhibitory factor on substance P, calcitonin gene-related peptide, vasoactive intestinal polypeptide and somatostatin expression in rat dorsal root ganglion cultures. As with neurons from adult animals, newborn rat sensory neurons required nerve growth factor for synthesis of substance P and calcitonin gene-related peptide. This effect was independent of neuronal survival since most neurons capable of expressing these peptides appeared to survive without added neurotrophic factors. Neurons surviving in the absence of nerve growth factor also expressed vasoactive intestinal polypeptide, suggesting that nerve growth factor suppresses vasoactive intestinal polypeptide expression in immature neurons. However, nerve growth factor withdrawal after eight days' culture failed to cause vasoactive intestinal polypeptide induction which therefore appears to depend on other factors also. Neither ciliary neurotrophic factor nor leukaemia inhibitory factor affected peptide levels when used alone, but both inhibited nerve growth factor-stimulated expression of substance P and calcitonin gene-related peptide in adult rat neurons. They also stimulated vasoactive intestinal polypeptide expression in newborn rat neurons in the presence of nerve growth factor but not to such high levels as those seen under conditions of nerve growth factor deprivation. Neither brain-derived neurotrophic factor nor neurotrophin-3 affected peptide expression significantly. Somatostatin was defected in adult rat neurons, but was unaffected by neurotrophic factors. No somatostatin was detected in newborn rat neurons. These results suggest that in immature animals at least, the increased expression of vasoactive intestinal polypeptide seen in sensory neurons following peripheral nerve injury in vivo, could result from deprivation of target-derived nerve growth factor in combination with increased availability of ciliary neurotrophic factor or leukaemia inhibitory factor from the injured nerve.
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PMID:Neuropeptide expression by newborn and adult rat sensory neurons in culture: effects of nerve growth factor and other neurotrophic factors. 751 8

The neurotransmitter phenotype switch that occurs in cultures of rat superior cervical ganglion neurons after treatment with leukemia inhibitory factor or ciliary neurotrophic factor is a useful model permitting investigation of the mechanisms of cytokine-mediated differentiation. Recently the actions of leukemia inhibitory factor and ciliary neurotrophic factor have been linked through their interactions with related receptor complexes. Here we compare the effects of these two cytokines on gene expression in sympathetic neuronal cultures and begin to investigate their mechanisms. We report that, as has been shown for leukemia inhibitory factor, ciliary neurotrophic factor regulates peptides and classical transmitters in these cultures at the mRNA level. In addition, we find that the induction of substance P mRNA by these cytokines is rapid, dependent on protein synthesis, and occurs in 40-50% of superior cervical ganglion neurons in dissociated culture.
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PMID:Coordinate regulation of choline acetyltransferase, tyrosine hydroxylase, and neuropeptide mRNAs by ciliary neurotrophic factor and leukemia inhibitory factor in cultured sympathetic neurons. 751 94

Interleukin-1 (IL-1) induction of substance P (SP) in cultured sympathetic ganglia requires a soluble intermediate molecule that is present in IL-1 conditioned medium (IL-1CM). One of the required intermediates is leukemia inhibitory factor (LIF; Shadiack et al., J Neurosci 13:2601-2609, 1993). In the present study we have examined the possibility that ciliary neurotrophic factor (CNTF) is another intermediate involved in the IL-1 induction of sympathetic SP. CNTF mimics the action of IL-1CM by raising both SP and choline acetyltransferase activity--actions that are blocked by a specific neutralizing antiserum for CNTF. However, IL-1CM and CNTF differ in their response to depolarizing agents: while KCl (40 mM) blocks the action of IL-1CM (and LIF), it enhances the action of CNTF. Furthermore, neither CNTF bioactivity nor CNTF protein is detected in IL-1CM. Neutralizing antiserum to CNTF fails to block the action of either IL-1 or IL-1CM, suggesting that neither a soluble nor a membrane-bound form of the molecule is active in direct response to IL-1 action. While Northern blots confirm the presence of both CNTF and CNTF receptor mRNA in neonatal ganglia, neither culturing nor IL-1 treatment alters these mRNA levels. These data taken together suggest that while CNTF is present and possibly active in sympathetic ganglia, it is not a mediator of the IL-1 induction of SP.
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PMID:The interleukin-1-induced increase of substance P in sympathetic ganglia is not mediated by ciliary neurotrophic factor. 752 14

Neural crest-derived cells populate the thymus, and their coexistence with epithelial cells is required for proper organ development and T cell education function. We show here that epidermal growth factor (EGF), a major epithelial cell growth-enhancing agent, has a morphogenetic action to promote the expression of a neuronal phenotype (e.g., neurofilament expression) in cultured thymic epithelial cells that are characterized by a cytokeratin-positive epithelial cell background. The proliferation of such neurodifferentiated cells is also enhanced by EGF. Furthermore, the growth factor enhances cells that express the genes encoding the preprotachykinin A-generated neuropeptides and bipotential neuropoietic and lymphopoietic cytokines ciliary neurotrophic factor and interleukin-6. These cytokines also enhance the neuronal phenotype of thymic epithelial cells. Therefore, EGF appears to be a composite autocrine/paracrine neuromodulator in thymic stroma. This suggests that EGF may regulate thymus-dependent immune functions by promoting neuronal gene expression in neural crest-derived cells.
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PMID:Epidermal growth factor promotes a neural phenotype in thymic epithelial cells and enhances neuropoietic cytokine expression. 754 Jun 16

The effect of interleukin (IL)-6 on cell survival, and the expression of choline acetyltransferase (ChAT) and neuropeptide mRNAs was examined in cultured rat sympathetic neurons. Reverse transcription-polymerase chain reaction analysis indicated that IL-6 treatment led to six-fold increase in ChAT mRNA without a concomitant increase in ChAT immunoreactivity. In contrast, treatment with ciliary neurotrophic factor or leukemia inhibitory factor/cholinergic differentiation factor increased ChAT mRNA levels 25-fold and resulted in intense ChAT immunoreactivity. Moreover, the latter factors increased somatostatin and preprotachykinin mRNA levels 10-fold whereas IL-6 had no effect. Maximal doses of IL-6 had no effect on cell survival. These findings provide a basis for the overlapping and yet divergent actions of these three factors which share some components of their signal transduction machinery.
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PMID:IL-6 increases choline acetyltransferase but not neuropeptide transcripts in sympathetic neurons. 791 55

We describe an assay based on reverse transcription-polymerase chain reaction to detect the expression of mRNAs for a variety of transmitter synthetic enzymes and neuropeptides present at low levels in primary neuronal cultures. The assay is specific for mRNA-derived templates and is not affected by the presence of genomic DNA. Using this method, we demonstrate that cholinergic differentiation factor/leukemia inhibitory factor (CDF/LIF) and ciliary neurotrophic factor (CNTF) induce mRNAs for choline acetyltransferase, somatostatin, substance P, vasoactive intestinal polypeptide, cholecystokinin, and enkephalin. The induction of cholecystokinin and enkephalin by CDF/LIF and CNTF had not been shown previously. These data illustrate that the assay can reproduce findings obtained with other methods, as well as provide the sensitivity necessary to produce new results. These results also extend the overlap of CDF/LIF and CNTF in controlling gene expression in cultured sympathetic neurons, supporting the idea that these cytokines may share receptor subunits and signal transduction pathways.
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PMID:A novel approach to screen for cytokine effects on neuronal gene expression. 810 31

The src homology 2 (SH2) domain-containing protein-tyrosine phosphatase SHP-2 has been implicated as an important positive regulator of several mitogenic signaling pathways. SHP-2 has more recently been shown to be tyrosine phosphorylated and recruited to the gp130 component of the ciliary neurotrophic factor (CNTF) receptor complex upon stimulation with CNTF. CNTF does not, however, have a proliferative effect on responsive cells, but rather enhances the survival and differentiation of sympathetic, motor, and sensory neurons. In this study, expression of an interfering mutant of SHP-2 in the neuroblastoma cell line NBFL increased CNTF induction of a vasoactive intestinal peptide (VIP) reporter gene, and in cultures of sympathetic neurons, it resulted in an up-regulation of endogenous VIP and substance P (SP) gene expression. Members of the CNTF family of cytokines transmit their signal by activating signaling pathways involving both STAT and Fos-Jun transcription factors. In CNTF-stimulated NBFL cells that constitutively express the SHP-2 interfering mutant, there was increased and prolonged formation of STAT/DNA complexes, but decreased AP-1 binding activity, that mirrored a down-regulation of c-fos expression both at the mRNA and protein level. Taken together, these data indicate that SHP-2 has dual and opposing roles in a signaling cascade triggered by the same ligand, as illustrated by its ability to differentially regulate the levels of activity of both STAT and AP-1 transcription factors.
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PMID:Coordinate regulation of STAT signaling and c-fos expression by the tyrosine phosphatase SHP-2. 949 48


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