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)

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

Neuronal precursor cells present in dorsal root ganglia (DRG) during early development have been previously shown to differentiate in vitro to neurons, as characterized by morphology, cell surface antigens, and electrophysiological properties (H. Rohrer, S. Henke-Fahle, T. El-Sharkawy, H. D. Lux, and H. Thoenen, 1985, Embo J. 4, 1709-1714). In the present study the conditions necessary for the initial differentiation and long-term survival of these cells were established, and the neurotransmitter phenotype of the newly differentiated neurons was analyzed. Neuronal precursor cells isolated from chick DRG at Embryonic Day 6 (E6) were found to require the presence of a polyornithine substrate coated with either laminin or fibronectin for initial neurite production and long-term survival. Neurons were unable to develop on polyornithine alone or on polyornithine coated with BSA. The survival and neurite outgrowth from neuronal precursor cells was not affected by the presence of nerve growth factor (NGF) during the first 9 hr in culture. NGF also had no effect on the proportion of cells expressing the neuron-specific Q211 antigen. However, after this initial differentiation period the neurons did require the presence of a survival factor. The neurons could be maintained for at least 6 days in culture both in the presence of NGF and in the presence of brain-derived neurotrophic factor (BDNF). At saturating concentrations of both survival factors no additive effects could be observed, indicating a complete overlap of NGF- and BDNF-responsiveness. Although the same proportion of cells survived with either NGF or BDNF during the first 3 days in culture, survival decreased in the presence of BDNF but not in the presence of NGF during the following 3 days in culture. The loss of BDNF responsiveness in vitro was also observed in vivo. After 6 days in culture about 70% of the neurons expressed substance P immunoreactivity, and approximately the same proportion was positive for myelin-associated glycoprotein immunoreactivity. The neurons did not express properties of adrenergic neurons such as tyrosine hydroxylase immunoreactivity or norepinephrine uptake. These findings indicate that the neuronal precursor cells from E6 DRG acquire the same characteristics in vitro as in their normal in vivo environment.
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PMID:Neuronal precursor cells in chick dorsal root ganglia: differentiation and survival in vitro. 245 Jul 97

We investigated the production, binding to cell membranes, and influence on cell proliferation of peptides and growth factors in 4 classic, 5 transitional, and 5 variant SCLC cell lines. Glucagon, neurotensin, and TGF-alpha were present in all cell lines. Bombesin was predominantly found in classic cell lines and insulin in variant cell lines. Neurokinin A, calcitonin, CGRP, GHRF, somatostatin, and CNTF were detectable in some cell lines without prevalence for a particular cell type. We could not detect AVP, growth hormone, neuropeptide Y, substance P, VIP, and NGF. Insulin binding sites were present on 11/14 cell lines, and some cell lines specifically bound bombesin, calcitonin, and EGF. Growth effects were detectable for insulin, GRP-related peptides, tachykinins, and VIP. Using serum-free conditions, insulin and VIP had a growth stimulating effect in liquid culture at nanomolar concentrations. Bombesin and neuromedin B stimulated the clonal growth at a concentration of 3-30 nM. The tachykinins neurokinin A, neurokinin B, physalaemin, and eledoisin inhibited the clonal and mass culture growth with a peak effect in the range of 0.1 to 10 pM. Peptide-induced stimulating and inhibiting effects were within a magnitude of 2-fold. All other peptides and growth factors tested, including ACTH, AVP, calcitonin, glucagon, neurotensin, somatostatin, EGF, CNTF, and NGF did not affect the growth of SCLC. We conclude that the growth of SCLC is partly controlled by such peptides in an autocrine/paracrine fashion.
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PMID:Peptides and growth factors in small cell lung cancer: production, binding sites, and growth effects. 283 87

We have previously reported the isolation of an EGF-responsive precursor from the embryonic and adult mouse striatum. This precursor exhibits self renewal and the ability to produce a sphere of undifferentiated cells which can be induced to differentiate into neurons and glia. RT-PCR analysis of these spheres of undifferentiated cells revealed the expression of mRNA for the trkB neurotrophin receptor, both with and without the catalytic domain, and little or no expression of trkA or trkC. We examined the actions of BDNF on the fate of EGF-generated neural precursors. Ten days after a one-time exposure to BDNF, single EGF-generated spheres showed a twofold increase in neuron number and a marked enhancement in neurite outgrowth. Examination of neuronal nuclei with immunochemical probes for c-fos and bromodeoxyuridine revealed that the actions of BDNF were directly upon neuronal cells and did not involve division of neuronal precursors. The twofold increase in neuronal number due to BDNF, observed after 10 d in vitro, was significantly reduced after 21 d in vitro and was not apparent at 27 d in vitro. Quantitative analyses revealed that while repeated application of BDNF did not prevent the loss of neuron number over time, it did result in a significant increase in neurite numbers. Moreover, delayed addition of BDNF mimicked the increase in neuronal numbers seen when BDNF was present throughout. These BDNF actions did not appear to involve the enhancement of a novel neuronal phenotype, with all effects being due to increase in the numbers and neurite outgrowth of neurons that colocalize GABA and substance P. These findings suggest that BDNF markedly enhances the antigenic and morphologic differentiation of EGF-generated neuronal precursors. BDNF alone does not appear to act as a survival factor for neuronal precursors nor is it sufficient for preventing their death over time.
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PMID:BDNF enhances the differentiation but not the survival of CNS stem cell-derived neuronal precursors. 764 17

Ciliary neurotrophic factor (CNTF) has a variety of effects on different neuronal populations in vitro, but little has been reported concerning its effects in vivo. This study examined the effects of CNTF administration on peripheral nerves both in young growing rats and in more mature animals. In both young and fully grown rats, CNTF stimulated levels of substance P and calcitonin gene related peptide in sensory spinal ganglia. In immature rats, CNTF increased compound nerve conduction velocity and motor nerve conduction velocity. By contrast, electrophysiological measurements were not affected in fully grown animals. There was a biphasic dose response to CNTF for the electrophysiologic changes with larger changes noted at a dose of 0.1 micrograms/g body weight than at a dose of 0.25 micrograms/g. There were no behavioral changes noted at either dose of the factor. These observations indicate that CNTF administration in vivo can influence neural physiology, and suggest that the factor may be useful for the treatment of disorders involving either sensory or motor peripheral nerves.
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PMID:Effects of administration of ciliary neurotrophic factor on normal motor and sensory peripheral nerves in vivo. 768 42

We examined 101 sera from 32 adult sporadic amyotrophic lateral sclerosis (ALS) patients, including nine with positive enzyme-linked immunosorbent assay (ELISA) serum antibodies against human spuma retrovirus (HSRV) [human foamy virus (HFV)] envelope (env) and/or capsid (gag) proteins, for peptide seroreactivity. Synthetic peptides 10 to 14 amino acids in length were selected from HSRV (3), maedi-visna virus (1), human nerve growth factor-beta (1), and human amyloid-beta sequences (1). Eighteen of 101 ALS sera compared with six of 144 control sera reacted to any of the sequences (p < 0.01) (i.e., 8/32 ALS patients and 2/93 control patients bound to a synthetic peptide, p < 0.01). Peptide VLA- [NGF beta(1-14)] was reproducibly recognized by one of the 93 neurologic controls, and one of the 32 ALS patients reproducibly reacted to synthetic peptides [EET-, HSRVenv/NGF beta(55-61)] and [GSN-, beta-amyloid(25-35)] simultaneously. This amyloid-A(25-35) peptide corresponds to the neurotoxic and neurotrophic tachykinin homology sequence described by Yanker. Only ALS patients (no controls) reacted with the visna/CNTF peptide SMC- and HSRVbcl-1/amyloid(740-751) peptide EGP-. Testing a total of 245 sera from 125 patients, three reproducible reactivities (two ALS, one OND) were observed both with and without glutaraldehyde linkage. Of the four peptides recognized either by more than one serum from the same patient with ALS or by sera from ALS patients only (EET-, GSN-, SMC-, EGP-), two share a circumscript homology with maedi-visna virus envelope glycoprotein (Table 1).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Retroviral synthetic peptide serum antibodies in human sporadic amyotrophic lateral sclerosis. 800 25

To develop an animal model of Alzheimer's disease, beta-amyloid protein was infused into the rat cerebral ventricle for 14 days using a mini-osmotic pump. The performance of some memory tasks in the beta-amyloid protein-treated rats was impaired. Long-term potentiation in the hippocampus was impaired in beta-amyloid-infused rats. The impairment of memory under the infusion could be recovered by two cognitive enhancer drugs. Choline acetyltransferase activity significantly decreased in the frontal cortex and hippocampus but glial fibrillary acidic protein immunoreactivity increased in the cortex both immediately and 2 weeks after cessation of the infusion. Ciliary neurotrophic factor contents in several brain areas in beta-amyloid-infused rat significantly increased. Substance P and microtubule-associated protein, which play an important role in neuronal transmission and construction of neuronal cells, respectively, decreased. Moreover, the release of acetylcholine and dopamine from the cortex/hippocampus and striatum, respectively, in the beta-amyloid-infused rats after depolarization was smaller than that from the control rats. These results suggest that beta-amyloid protein induced dysfunction of the central nervous system in vivo, and that the animal could be used as a model of Alzheimer's disease.
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PMID:[Experimental techniques for developing new drugs acting on dementia (10)--Alzheimer's disease animal model induced by beta-amyloid protein]. 890 95

Pain induced by bone metastases has a strong impact on the quality of life of patients with cancer, but current therapies for bone cancer pain cannot attain a satisfactory therapeutic goal because of various adverse reactions. Currently, advanced monitoring is required to clarify pathogenic mechanisms, so as to develop more effective treatments. We constructed herpes simplex virus carrying small interference RNA for CNTF (HSV-siCNTF) and established cancer-induced bone cancer pain models with intra-tibial injection of MRMT-1 cells. At different time points after treatment, sensory function indicated by thermal hyperalgesia and mechanical allodynia was measured. The mechanism underlying sensory function regulated by CNTF was also determined. There was apparent mechanical and thermal hyperalgesia in rats injected with bone cancer cells. Bone destruction was detected in the area of tibia injected with tumor cells by the plain radiography. MRMT-1 cells and the increased number of osteoclasts were found in tibia sections stained with hematoxylin and eosin. Intrathecal injection of morphine or HSV-siCNTF significantly reduced the mechanical allodynia and thermal hyperalgesia, which was accompanied by astrocyte hypertrophy. The number of nerve fibers positive for substance P (SP) and calcitonin gene related peptide (CGRP) was significantly decreased, which was consistent with the decrease of CNTF, ERK/pERK, AKT/pAKT and c-fos expression. These results demonstrate that the HSV-siCNTF gene therapy appears beneficial for the treatment of pain induced by bone cancer via blocking the AKT-ERK signaling pathway. Our data suggest that CNTF interference may be considered a new target to develop an effective management for bone cancer pain.
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PMID:Reversal of bone cancer pain by HSV-1-mediated silencing of CNTF in an afferent area of the spinal cord associated with AKT-ERK signal inhibition. 2568 3