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)

Substance P and calcitonin gene-related peptide (CGRP) released from primary sensory neurons are known to play important roles in nociception and nociceptive transmission. In the present study, we attempted to clarify the roles of these neuropeptides in the regulation of axonal transport in sensory neurons. Cells were isolated from adult mouse dorsal root ganglia and cultured in F-12 medium containing fetal bovine serum for 48 h until their neurites were grown. These isolated and cultured DRG cells were mostly (>98%) small (diameter <25 microm) and medium (diameter, 25-40 microm) in size, and were immunoreactive for substance P and CGRP (85.9 and 66. 0% of total cells, respectively). Video-enhanced microscopy was applied to observe particles transported within neurites. Application of substance P (100 nM) decreased the number of particles transported in both anterograde and retrograde directions in each of DRG neurons tested (n=5). The instantaneous velocities of individual particles transported in anterograde and retrograde directions were also reduced by substance P. In contrast, alpha-CGRP (100 nM) increased the number of particles transported in both directions in each of DRG neurons tested (n=5), and also increased the instantaneous velocities of particles transported bidirectionally. Application of beta-CGRP (100-1000 nM) did not elicit any effect on axonal transport. Therefore, axonal transport in sensory neurons seems to be modulated by substance P and alpha-CGRP, both of which can be derived from its own and adjacent sensory neurons.
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PMID:Effects of substance P and calcitonin gene-related peptide on axonal transport in isolated and cultured adult mouse dorsal root ganglion neurons. 1107 47

Gene expression of somatostatin (SST) and preprotachykinin A (PPTA) in lumbar DRG neurons of postnatal developing rats was examined by in situ hybridization. SST mRNA signals were not seen in DRG neurons until postnatal day 1 to 7, and were detected in about 10% of DRG neurons of 2- and 8-week-old rats. The positive neurons expressed c-ret mRNA in 8-week-old rats. On the other hand, PPTA mRNA signals were constantly seen in about 30% of DRG neurons. This study demonstrates the differential expression patterns of SST and PPTA mRNAs in DRG neurons of developing rats.
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PMID:Delayed expression of somatostatin mRNA in GDNFs-dependent rat sensory neurons during postnatal development. 1115 70

Animal models for human chronic pain syndromes have been developed and widely used for pain research. One of these neuropathic pain models by Kim and Chung (1992) has many advantages for operation and pain elicitation. In this neuropathic model we have examined the c-fos protein, substance P, CGRP immunoreactivity in dorsal root ganglia and dorsal horn. 50 Sprague-Dawley rats were used for this study. L5 and L6 spinal nerves were ligated tightly to produce the neuropathic pain model. After 2, 4, 8, 16, and 24 hours and 1 week of surgery, rats were anesthetized and sacrificed by perfusion. After confirmation of the roots transected by the surgery, the L5 and L6 dorsal root ganglions and spinal cord were removed and processed for immunohistochemistry. All tissue sections were immunohistochemically stained for substance P, CGRP and c-fos using the peroxidase-antiperoxidase (PAP) method. The number of immunostained substance P and CGRP dorsal root ganglion cells and c-fos immunoreactive dorsal horn cells were counted and analyzed statistically with Mann-Whitney U test. The results are as follows. The number of c-fos protein immunoreactive neurons in the superficial layer of dorsal horn were increased markedly 2 hours after operation, and gradually decreased to normal level 1 week after operation. The number of c-fos protein immunoreactive neurons in the deep layer of the dorsal horn gradually increased to a peak 24 hours after operation, then decreased to the normal level 1 week after operation. The number of substance P and CGRP immunoreactive L5 and L6 dorsal root ganglion neurons were decreased markedly 1 week after the pain model operation. In conclusion, after neuropathic pain model operation, c-fos proteins were immediately expressed in the superficial layer of spinal dorsal horn, thereafter c-fos proteins in the deep layer of spinal dorsal horn were expressed. CGRP and substance P immunoreactive neurons in DRG were decreased markedly 1 week after neuropathic pain model operation. These decrements do not coincide with the other chronic pain models, which show great increases in these pain transmitting substances. Therefore, the relationship between pain and c-fos, SP and CGRP should be investigated further.
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PMID:Studies on the changes of c-fos protein in spinal cord and neurotransmitter in dorsal root ganglion of the rat with an experimental peripheral neuropathy. 1129 99

These studies examined changes in the expression of calcitonin gene-related peptide (CGRP) and substance P (SP) in lumbosacral (L6-S1) micturition reflex pathways, following chronic cystitis induced by cyclophosphamide (CYP). In control Wistar rats, CGRP- or SP-immunoreactivity (IR) was expressed in fibers in the superficial dorsal horn in all segmental levels examined (L4-S1). Bladder afferent cells in the dorsal root ganglia (DRG; L6, S1) from control animals also exhibited CGRP- (41-55%) or SP-IR (2-3%). Following chronic, CYP-induced cystitis, CGRP- and SP-IR were dramatically increased in spinal segments and DRG (L6, S1) involved in micturition reflexes. The density of CGRP- and SP-IR was increased in the superficial laminae (I-II) of the L6 and S1 spinal segments. No changes in CGRP- or SP-IR were observed in the L4-L5 segments. Staining was also dramatically increased in a fiber bundle extending ventrally from Lissauer's tract in lamina I along the lateral edge of the DH to the sacral parasympathetic nucleus in the L6-S1 spinal segments. Following chronic cystitis, CGRP- and SP-IR in cells in the L6 and S1 DRG significantly (P< or =0.05) increased and the percentage of bladder afferent cells expressing CGRP- (76%) or SP-IR (11-18%) also significantly (P< or =0.001) increased. No changes were observed in the L4-L5 DRG. These studies suggest that the neuropeptides, CGRP and SP, may play a role in urinary bladder afferent pathways, following chronic urinary bladder inflammation. Changes in CGRP or SP expression following cystitis may contribute to the altered visceral sensation (allodynia) and/or urinary bladder hyperreflexia in the clinical syndrome, interstitial cystitis.
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PMID:Alterations in neuropeptide expression in lumbosacral bladder pathways following chronic cystitis. 1131 54

The rat L5/6 disc is innervated from T13 to L6 dorsal root ganglia (DRGs) multisegmentally. Sensory fibers from T13, L1 and L2 DRGs have been reported to innervate through the paravertebral sympathetic trunks, whereas those from L3 to L6 DRGs innervate directly through sinuvertebral nerves on the posterior longitudinal ligament (PLL). The presence of substance P (SP)- and calcitonin gene-related peptide (CGRP)-immunoreactive (ir) nerve fibers has been demonstrated in the lumbar intervertebral discs, but their percentages in DRG neurons have not been studied. Fluoro-gold (F-G) labeled neurons innervating the L5/6 disc were distributed throughout DRGs from T13 to L6 levels. Of F-G labeled neurons innervating the L5/6 disc, the percentage of SP-ir T13 to L6 DRG neurons was 30%, and that of CGRP-ir neurons was 47%. The mean cross-sectional area of the cell of SP-ir neurons was 696+/-66 microm2 (mean +/- S. E.), and that of CGRP-ir neurons was 695+/-72 microm2 (mean +/- S. E.). SP- and CGRP-ir were mainly observed in small neurons. The percentages of SP- or CGRP-ir neurons in L1 and L2 DRGs innervating the L5/6 disc were not different from those in L3, L4 or L5 DRGs. In the physiological condition in rats, DRG neurons at all levels may have the same significant role in pain sensation of the disc.
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PMID:Substance P and calcitonin gene-related peptide immunoreactive sensory DRG neurons innervating the lumbar intervertebral discs in rats. 1205 53

We hypothesize that the transcription factor neuron restrictive silencer factor (NRSF) is an important determinant of the expression of the preprotachykinin (PPTA) gene (encoding substance P and Neurokinin A) and arginine vasopressin (AVP) both in neuronal and nonneuronal cells. NRSF, a zinc finger repressor protein, binds the NRSE motif found in many neuronal specific genes at a variety of promoter locations. However, it is found in a similar location at the major transcriptional start site, within both PPTA and AVP peptide promoters. We have correlated modulation of NRSF activity with expression of AVP and PPTA in a variety of cell types, indicating the general mechanism by which this protein may regulate expression. Specifically, they are as follows:(1). Expression of NRSF dramatically represses PPTA promoter activity in reporter gene constructs in primary cultures of DRG neurons.(2). The PPTA promoter activity is regulated differentially in osteoarthritic compared to normal chondrocytes. This regulation correlates with the region containing the NRSE site.(3). We have correlated a splice variant of NRSF with the establishment and progression of small cell lung carcinoma (SCLC) and demonstrated that NRSF variants can directly affect the activity of the AVP promoter in reporter gene constructs. If the deregulated expression of peptides in these diseases point to the mechanism determining the pathology, then perhaps targeting protocols that correct this deregulation may also reverse the specific disease phenotypes. Our data would indicate that modulation of NRSF activity would be a target for such intervention.
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PMID:Neuron restrictive silencer factor as a modulator of neuropeptide gene expression. 1222 Jul 37

Peripheral nerve transection in the rat alters the spinal cord dorsal horn central projections from both small and large DRG neurons. Injured neurons with C-fibers exhibit transganglionic degeneration of their terminations within lamina II of the spinal cord dorsal horn, while peripheral nerve injury of medium to large neurons induces collateral sprouting of myelinated A-fibers from lamina I and III/IV into lamina II in rats, cats, and primates. To date, it is not known what sequelae are responsible for the collateral sprouting of A-fibers after peripheral nerve injury, although target-derived factors are thought to play an important role. To determine whether target-derived factors are necessary for changes in A-fiber laminar terminations in rat spinal cord dorsal horn, we unilaterally transected the sciatic nerve and ensheathed the proximal nerve stump in a silicone cap. Three days before sacrifice of rat, the injured sciatic nerve was injected with cholera toxin beta-subunit conjugated to horseradish peroxidase (betaHRP) that effectively labels both peripheral and central A-fiber axons. The effect of the ligature, axotomy, and silicone cap treatment was evaluated by analyzing the extent of betaHRP-, Substance P-(SP-), and isolectin B4- (IB4-) immunoreactive (ir) fibers in the somatotopically appropriate spinal cord dorsal horn regions. In all animals, 2-5 weeks after nerve transection (treated or otherwise), IB4- and SP-ir is absent from lamina II. Animals without nerve cap treatment exhibited robust fiber sprouting into lamina II at 2 weeks. In sharp contrast, animals treated with silicone caps did not exhibit betaHRP-ir fibers in lamina II at 2 weeks. This observation was extended up to 5 weeks postinjury. These results suggest that axotomy-induced expansion of betaHRP-ir primary afferent central terminations in the spinal cord dorsal horn is dependent on factors produced in the injury site milieu. While our understanding of local repair mechanisms of injured peripheral nerves is incomplete, it is clear that the time-dependent production of growth factors in the nerve injury microenvironment favor nerve fiber outgrowth, both peripherally and centrally.
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PMID:A-fiber sprouting in spinal cord dorsal horn is attenuated by proximal nerve stump encapsulation. 1242 85

We have previously shown (Gastroenterology, 101 (1991) 1211-1219), that substance P (SP) decreases early in the colon muscle layer after induction of colitis in rabbits. Since the SP content in the colonic muscle layer was unchanged by sensory denervation with capsaicin, we assume that SP is located predominantly in intrinsic neurons of the colon, and that the decrease of SP during inflammation reflects changes in intrinsic SP content. However, damage of SP neurons by inflammation would be another likely explanation for the decrease in SP content. The aim of this study was to determine SP gene expression in intrinsic (colonic muscle layer) and extrinsic (dorsal root ganglia, DRG) neurons to prove that SP transcription is preserved during colitis as an indicator of neuronal integrity. Colitis was induced in adult white New Zealand rabbits by formalin enemas (4 ml of 0.4% formalin) followed by 0.85 ml immune complex i.v. 2 h later. The animals were sacrificed 48 h after induction of colitis, and SP content and gene expression were determined by radioimmunoassay (RIA) and Northern blot analysis, respectively. Immunoreactive SP was reduced by 40% in the colon muscle layer and by 60% in the dorsal root ganglia (L4-S4) in the animals with colitis compared to controls without colitis. In contrast to the protein data, SP gene expression was not significantly altered in the colon muscle layer and the dorsal root ganglia 48 h after induction of inflammation compared to the control tissue. The preserved SP gene expression suggests that the intrinsic and extrinsic SP neurons are viable in this inflammatory model. The decreases of immunoreactive SP in the colonic extracts and the DRG after induction of colitis suggest that SP is released from extrinsic and intrinsic neurons during inflammation.
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PMID:Substance P gene expression in acute experimental colitis. 1250 14

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

Human dorsal root ganglia (DRGs) were obtained during various procedures and processed for single and double in situ hybridisation using oligonucleotide probes complementary to three peptide mRNAs. Some postmortem ganglia were also analysed. In donor (unlesioned) DRGs 12.5% of the neuron profiles (NPs) were galanin mRNA-positive (mRNA(+)), 47.5% calcitonin gene-related peptide (CGRP) mRNA(+) and 32.7% substance P mRNA(+). The corresponding percentages for cervical/thoracic DRGs from patients suffering from severe brachial plexus injury were 32.8%, 57.4% and 34.5%, respectively. In these DRGs a high proportion of the galanin mRNA(+) NPs contained CGRP mRNA and substance P mRNA. In DRGs from a patient with migraine-like pain a comparatively small proportion expressed galanin, whereas in DRGs from a herpes zoster patient galanin mRNA(+) NPs were comparatively more frequent. The results from human postmortem DRGs revealed only weak peptide mRNA signals. The present results demonstrate that galanin is expressed in DRGs not only in a number of animal species including monkey as previously shown, but also in a considerable proportion of human DRG neurons, often together with CGRP and substance P, and mostly in small neurons. Thus, galanin may play a role in processing of sensory information, especially pain, in human DRGs and dorsal horn. However, to what extent a similarly dramatic upregulation of galanin expression can be seen after peripheral nerve lesion in man, as has been reported for rat, mouse and monkey, remains to be analysed.
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PMID:Galanin expression in adult human dorsal root ganglion neurons: initial observations. 1265 33

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