UNIPROT:P20366 - FACTA Search

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Query: UNIPROT:P20366 (substance P)
21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The response of trunk neural crest cells taken from precise levels of the neural axis and cultured together with adjacent somites to Brain-derived neurotrophic factor (BDNF), was examined in cultures grown in a chemically defined medium. In control cultures, the number of neural crest-derived neurons expressing the HNK-1 epitope, increased as a function of somitic level in a caudorostral direction. Treatment of cultures with increasing concentrations of BDNF (50 pg/ml to 1 ng/ml) resulted in a 1.5- to 6-fold stimulation in the number of neurons developing from crest cells excised at advanced and post-migratory stages, whereas early migrating crest cells were responsive only to concentrations equal to or higher than 1 ng/ml of BDNF. Nerve growth factor used at 5 and 30 ng/ml had no effect on survival of HNK-1-positive cells at any of the somitic levels tested. In an attempt to identify the subpopulation of HNK-1-immunoreactive neurons responding to BDNF, control and treated cultures were stained for the HNK-1 antibody in combination with substance P (SP) antibodies (as a marker for sensory neurons). SP immunoreactivity localized to a subpopulation of phase-bright, HNK-1-positive neurons. The absolute number of SP-positive neurons increased 2- to 4-fold upon BDNF treatment; however, their relative proportion within the population expressing the HNK-1 epitope remained essentially unchanged from control to treated cultures (on day 1, 20% as compared to 23.3% and on day 2, 44.6% compared to 49.7% for control and treated cultures, respectively). Taken together, these data suggest that BDNF stimulates primary neuronal differentiation of SP expressing neurons, and/or their survival.
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PMID:Brain-derived neurotrophic factor stimulates survival and neuronal differentiation in cultured avian neural crest. 340 10

Brain-derived neurotrophic factor (BDNF) specifically enhances and maintains the expression of neuropeptide Y (NPY) and somatostatin (SOM) in cultured neocortical neurons (Nawa et al., 1993). In this article, we examined its effects in vivo on neuropeptide expression in various brain regions by injecting BDNF into the cerebroventricle of newborn rats. Repeated administration (2x) of BDNF increased contents of NPY-like immunoreactivity (NPY-LI) and substance P (SP)-LI most markedly in the anterior neocortex by 11- and 24-fold, respectively, in comparison to values in the animals receiving control injection. A smaller but significant increase was also observed in immunoreactivity for somatostatin (SOM), enkephalin (ENK), and cholecystokinin (CCK). mRNA for NPY, SP, and SOM was similarly upregulated in the anterior neocortex, suggesting that BDNF enhances peptide synthesis rather than inhibiting peptide release or degradation. Among the brain regions examined, however, peptidergic responses to BDNF were different with respect to their spatial distribution and time course. Induction of SP-LI, NPY-LI, and SOM-LI around the injection site was most pronounced in cortical layers II/III, layers IV-VI, and layer VI, respectively. Peptidergic immunoreactivity was also enhanced in other brain regions ipsilateral to the injection site, for example, NPY-LI in the hippocampus, thalamic nuclei, and striatum, and SOM-LI in the striatum. A single injection of BDNF elevated SP-LI to a plateau level within 12 hr while NPY-LI and SOM-LI reached maximum levels at 48 hr, and then all returned to control levels at 68 hr. In contrast, the same dose of NGF had no influences on the neuropeptide levels at 48 hr. These observations suggest that BDNF regulates the development of neuropeptide expression in the CNS in a plastic manner.
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PMID:Intraventricular administration of BDNF increases neuropeptide expression in newborn rat brain. 751 53

Neurotrophins, which are structurally related to nerve growth factor, have been shown to promote survival of various neurons. Recently, we found a novel activity of a neurotrophin in the brain: Brain-derived neurotrophic factor (BDNF) enhances expression of various neuropeptides. The neuropeptide differentiation activity was then compared among neurotrophins both in vivo and in vitro. In cultured neocortical neurons, BDNF and neurotrophin-5 (NT-5) remarkably increased levels of neuropeptide Y and somatostatin, and neurotrophin-3 (NT-3) also increased these peptides but required higher concentrations. At elevating substance P, however, NT-3 was as potent as BDNF. In contrast, NGF had negligible or no effect. Neurotrophins administered into neonatal brain exhibited slightly different potencies for increasing these neuropeptides: The most marked increase in neuropeptide Y levels was obtained in the neocortex by NT-5, whereas in the striatum and hippocampus by BDNF, although all three neurotrophins increased somatostatin similarly in all the brain regions examined. Overall spatial patterns of the neuropeptide induction were similar among the neurotrophins. Neurons in adult rat brain can also react with the neurotrophins and alter neuropeptide expression in a slightly different fashion. Excitatory neuronal activity and hormones are known to change expression of neurotrophins. Therefore, neurotrophins, neuronal activity, and hormones influence each other and all regulate neurotransmitter/peptide expression in developing and mature brain. Physiological implication of the neurotransmitter/peptide differentiation activities is also discussed.
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PMID:Regulation of neuropeptide expression in the brain by neurotrophins. Potential role in vivo. 757 4

Spinal cord projections from transected sciatic nerves treated with different neurotrophins were investigated in the adult rat following injections of choleragenoid into the proximal stump of the injured nerve. Transganglionically transported choleragenoid labelled primary afferent fibres in all spinal cord dorsal horn laminae except the outer part of lamina II (II(o)), which is almost devoid of labelling. Transection of the sciatic nerve, however, resulted in intense transganglionic choleragenoid labelling in lamina II(o) and in lamina I. In this study, the sciatic nerve was transected bilaterally and 4erve growth factor (6 or 24 microg), brain-derived neurotrophic factor (20 microg), neurotrophin-3 (27 microg) or cytochrome C (8 microg; control substance) was applied unilaterally during postoperative survival times of eight, 16 and 32 days. The animals received bilateral injections of choleragenoid into the injured nerve two days before they were killed. The effect of the axotomy and neurotrophin treatment was evaluated by analysing the extent of choleragenoid and substance P immunoreactivity in the somatotopically appropriate spinal cord dorsal horn regions. At eight days' postoperative survival, laminae I and II(o) on the transected, non-treated side showed much more intense choleragenoid-like immunoreactivity compared to the contralateral transected, nerve growth factor-treated (6 and 24 microg) side. A similar situation was also found in cases treated with the higher dose (24 microg) at 16 days but to a lesser degree when the lower (6 microg) dose was used. After 32 days' survival, there was no detectable side difference in the choleragenoid labelling pattern. At 16 days' survival, the mean area of choleragenoid-positive ganglion cell body profiles in the L5 dorsal root ganglion of the transected, non-treated side was significantly smaller than the mean area of the transected, nerve growth factor-treated (24 microg) neurons. An axotomy-induced depletion of substance P-like immunoreactivity was seen from eight days' survival and onwards, whereas on the nerve growth factor-treated side a clearcut substance P depletion was not observed until 32 days. Brain-derived neurotrophic factor, neurotrophin-3 and cytochrome C had no detectable effects on the distribution of choleragenoid labelling or substance P-like immunoreactivity in the dorsal horn following sciatic nerve transection. In conclusion, peripheral nerve injury-induced expansion of primary afferent choleragenoid labelling in the spinal cord dorsal horn is counteracted by treating the axotomized nerve with nerve growth factor.
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PMID:Effects of nerve growth factor, brain-derived neurotrophic factor and neurotrophin-3 on the laminar distribution of transganglionically fransported choleragenoid in the spinal cord dorsal horn following transection of the sciatic nerve in the adult rat. 915 64

To determine whether growth factors of the neurotrophin family are able to regulate the phenotype of striatal projection neurons, cell lines overexpressing brain-derived neurotrophic factor, neurotrophin-3 or neurotrophin-4/5 were intrastriatally grafted. Striatal projection neurons were examined for the regulation of their soma areas and for the expression of glutamate decarboxylase 67, preprotachykinin A, preproenkephalin and prodynorphin messenger RNAs by in situ hybridization. Brain-derived neurotrophic factor, neurotrophin-3 and neurotrophin-4/5 differentially regulated the soma area of projection neurons at different distances from the graft, but did not modify their messenger RNA levels. Neurotrophin-3 induced an increase in the soma area of preproenkephalin- and preprotachykinin A-positive neurons, brain-derived neurotrophic factor increased the soma area of only preprotachykinin A-positive neurons, while neurotrophin-4/5 did not produce any effect. Because atrophy and neuronal loss are hallmarks of Huntington's disease, we next examined whether neurotrophins prevent degenerative changes in a quinolinate model of Huntington's disease. Seven days after intrastriatal quinolinate injection, we observed a halo of cell loss around the injection sites, reduced soma area of glutamate decarboxylase 67-, preproenkephalin- and preprotachykinin A-positive neurons bordering the lesion, and a decrease in the messenger RNA levels of glutamate decarboxylase 67 and these neuropeptides. Grafting of cell lines expressing brain-derived neurotrophic factor, neurotrophin-3 or neurotrophin-4/5 reduced the size of the lesion for preproenkephalin-, preprotachykinin- and glutamate decarboxylase 67-, but not for prodynorphin-positive neurons. Moreover, the three neurotrophins prevented the atrophy of all projection neurons, and the lesion-induced decrease in preproenkephalin and preprotachykinin A messenger RNA levels. We conclude that neurotrophins differentially regulate the phenotype of striatal projection neurons and prevent degenerative changes. The higher efficiency of neurotrophin-3 suggests a potential therapeutic application of this molecule in neurological disorders affecting striatal projection neurons, such as Huntington's disease.
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PMID:Brain-derived neurotrophic factor, neurotrophin-3 and neurotrophin-4/5 differentially regulate the phenotype and prevent degenerative changes in striatal projection neurons after excitotoxicity in vivo. 1039 33

Brain-derived neurotrophic factor (BDNF) can produce hyperalgesia in the adult rat. Here we assessed whether changes in the spinal release of the nociceptive peptide substance P (SP) contributes to this effect. Antibody-coated microprobes revealed a significant basal release of SP in the dorsal horn in vivo that was increased following acute knee inflammation. Microinjection of BDNF into the grey matter (0.5 microl, 10(-5) M) altered SP release neither in rats with normal knees nor in rats with inflamed knee joints. In the lumbar dorsal horn slice preparation in vitro, superfusion with BDNF (100 ng/ml) could reduce SP release evoked by electrical dorsal root stimulation without modyfing SP basal outflow. It is unlikely, therefore, that enhanced spinal SP release mediates the hyperalgesic effect of BDNF.
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PMID:Effect of brain-derived neurotrophic factor on the release of substance P from rat spinal cord. 1120 Oct 84

Brain-derived neurotrophic factor (BDNF) is synthesized by small neuron cell bodies in the dorsal root ganglia (DRG) and is anterogradely transported to primary afferent terminals in the dorsal horn where it is involved in the modulation of painful stimuli. Here we show that BDNF is released in the rat isolated dorsal horn after chemical stimulation by capsaicin or electrical stimulation of dorsal roots. Capsaicin superfusion (1-100 microm) induced a dose-dependent release of BDNF, measured using ELISA. The highest dose of capsaicin also induced a depletion of BDNF protein in the dorsal horn. BDNF release was also seen after electrical stimulation of the dorsal roots at C-fiber strength. This release was encoded by specific patterns of afferent fiber stimulation. Neither continuous low-frequency (480 pulses, 1 Hz) nor tetanic high-frequency (300 pulses in 3 trains, 100 Hz) stimulation evoked release of BDNF, although substance P (SP) release was observed under both of these conditions. However, BDNF was released after short bursts of high-frequency stimulation (300 pulses in 75 trains, 100 Hz) along with SP and glutamate. The NMDA antagonist d-AP-5 inhibited electrically evoked BDNF release. BDNF release was also measured after systemic or intrathecal NGF treatment. This upregulated BDNF content in the DRG and increased the capsaicin-evoked release of BDNF. Similarly, the amount of BDNF released by burst stimulation was increased after NGF treatment. This activity-dependent release continued to be encoded solely by this stimulation pattern. These experiments demonstrate that BDNF release in the dorsal horn is encoded by specific patterns of afferent fiber stimulation and is mediated by NMDA receptor activation.
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PMID:Brain-derived neurotrophic factor is released in the dorsal horn by distinctive patterns of afferent fiber stimulation. 1140 34

The rat L5/6 intervertebral disc is innervated by L1 to L6 dorsal root ganglia (DRGs). T13 to L2 DRGs innervate the L5/6 intervertebral disc through paravertebral sympathetic trunks, whereas L3 to L6 DRGs directly innervate through sinuvertebral nerves on the posterior longitudinal ligament. The presence of substance P (SP)-immunoreactive (ir) and calcitonin gene-related peptide (CGRP-ir) sensory nerve fibers on the lumbar intervertebral disc has been established. SP and CGRP are markers of sensory neurons mainly involved with pain perception. The existence of SP-ir and CGRP-ir DRG neurons innervating the L5/6 intervertebral disc has been also demonstrated. Brain-derived neurotrophic factor (BDNF), which exists mainly in the small DRG neurons, plays an important neuromodulatory role in inflammatory conditions. Vanilloid receptor subtype 1 (VR1) in the DRG neurons and spinal dorsal horn is a channel that appears to confer responsiveness to heat and chemical stimuli. The presence of BDNF-ir and the VR1-ir DRG neurons innervating the L5/6 intervertebral disc has not. In this study of DRG neurons innervating the L5/6 intervertebral disc, the proportions of BDNF-ir in L1, L2, L3, L4, and L5 DRG neurons were 14%, 12%, 12%, 12%, and 13% and the proportions of VR1-ir L1, L2, L3, L4, and L5 DRG neurons were 10%, 8%, 24%, 19%, and 23%, respectively. Under physiological conditions in rats these neurons may transmit inflammatory and burning pain of the L5/6 intervertebral disc.
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PMID:Existence of brain-derived neurotrophic factor and vanilloid receptor subtype 1 immunoreactive sensory DRG neurons innervating L5/6 intervertebral discs in rats. 1256 Aug 92

Brain-derived neurotrophic factor (BDNF) is a key modulator during the development of jugular and nodose ganglia neurons, which represent the origin of a large proportion of the sensory innervation of the lung. It belongs to the family of neurotrophins, which have been shown to induce the expression of tachykinins. To assess the interactions of BDNF and the tachykinin neurokinin A (NKA) in small pulmonary vessels, BDNF-transgenic mice were examined for tachykinin contents in the airways, heart, trigeminal ganglion and jugular and nodose ganglion complex (JNC) using reverse phase HPLC (rpHPLC) and radioimmunoassay. BDNF-overexpression led to increased NKA levels in the heart and the JNC, whereas only slightly enhanced levels in the trigeminal ganglion were detected. Lower NKA levels were found in the lung. To assess vasoreactivity in small arteries, precision cut lung slices were subjected to videomorphometry and the response to NKA was examined, which showed significantly stronger effects in the BDNF-transgenic mice, while NK-2 receptor mRNA expression, assayed by real-time RT-PCR, was reduced. In conclusion, BDNF-overexpression results in decreased levels of NKA in the lung with subsequently increased NKA-sensitivity of small arteries. These findings point to a modulatory role of neurotrophins in small respiratory vessel tone regulation.
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PMID:BDNF-overexpression regulates the reactivity of small pulmonary arteries to neurokinin A. 1475 52

Manipulation of neurotrophin (NT) signalling by administration or depletion of NTs, by transgenic overexpression or by deletion of genes coding for NTs and their receptors has demonstrated the importance of NT signalling for the survival and differentiation of neurons in sympathetic and dorsal root ganglia (DRG). Combination with mutation of the proapoptotic Bax gene allows the separation of survival and differentiation effects. These studies together with cell culture analysis suggest that NT signalling directly regulates the differentiation of neuron subpopulations and their integration into neural networks. The high-affinity NT receptors trkA, trkB and trkC are restricted to subpopulations of mature neurons, whereas their expression at early developmental stages largely overlaps. trkC is expressed throughout sympathetic ganglia and DRG early after ganglion formation but becomes restricted to small neuron subpopulations during embryogenesis when trkA is turned on. The temporal relationship between trkA and trkC expression is conserved between sympathetic ganglia and DRG. In DRG, NGF signalling is required not only for survival, but also for the differentiation of nociceptors. Expression of neuropeptides calcitonin gene-related peptide and substance P, which specify peptidergic nociceptors, depends on nerve growth factor (NGF) signalling. ret expression indicative of non-peptidergic nociceptors is also promoted by the NGF-signalling pathway. Regulation of TRP channels by NGF signalling might specify the temperature sensitivity of afferent neurons embryonically. The manipulation of NGF levels "tunes" heat sensitivity in nociceptors at postnatal and adult stages. Brain-derived neurotrophic factor signalling is required for subpopulations of DRG neurons that are not fully characterized; it affects mechanical sensitivity in slowly adapting, low-threshold mechanoreceptors and might involve the regulation of DEG/ENaC ion channels. NT3 signalling is required for the generation and survival of various DRG neuron classes, in particular proprioceptors. Its importance for peripheral projections and central connectivity of proprioceptors demonstrates the significance of NT signalling for integrating responsive neurons in neural networks. The molecular targets of NT3 signalling in proprioceptor differentiation remain to be characterized. In sympathetic ganglia, NGF signalling regulates dendritic development and axonal projections. Its role in the specification of other neuronal properties is less well analysed. In vitro analysis suggests the involvement of NT signalling in the choice between the noradrenergic and cholinergic transmitter phenotype, in the expression of various classes of ion channels and for target connectivity. In vivo analysis is required to show the degree to which NT signalling regulates these sympathetic neuron properties in developing embryos and postnatally.
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PMID:Role of neurotrophin signalling in the differentiation of neurons from dorsal root ganglia and sympathetic ganglia. 1938 88

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