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

The peripheral reorganization of pulpal nerves after tooth injury was studied, in the rat, with anterograde horseradish peroxidase tracing techniques, and combined retrograde Fluorogold tracing and immunohistochemistry was employed to examine the effects of inferior alveolar nerve lesions or tooth injury on some cytochemical characteristics of pulpal trigeminal ganglion nerve cells, namely content of substance P, calcitonin gene-related peptide and the ganglioside GM1 (binding subunit of cholera toxin), as well as affinity to RT 97 (antibody to neurofilament protein) and the lectin Griffonia simplicifolia isolectin I-B4. Anterograde horseradish peroxidase tracing demonstrated that pulpal nerves either disappear or reinnervate novel targets after loss of pulpal tissue. There were no obvious signs of neuroma formation. Retrograde Fluorogold labelling with immunohistochemistry showed that after inferior alveolar nerve lesions with subsequent regeneration, a much higher proportion of Fluorogold cells (15%) were substance P-positive compared to normal (2%). In addition, 3% of the cells were Griffonia simplicifolia isolectin I-B4-positive. Such cells were very rare in controls. Proportions of calcitonin gene-related peptide-, GM1- and RT-97-positive cells were normal. After tooth lesions, the proportions of Fluorogold-positive substance P-, Griffonia simplicifolia isolectin I-B4-, GM1- and RT 97-labelled cells were similar to controls, while the proportion of calcitonin gene-related peptide-positive neurons was reduced. The results show that pulpal deafferentation may change the long-term cytochemical characteristics of affected trigeminal ganglion neurons.
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PMID:Anterograde horseradish peroxidase tracing and immunohistochemistry of trigeminal ganglion tooth pulp neurons after dental nerve lesions in the rat. 192 70

Localization of GM1 ganglioside, the receptor for cholera toxin, and choleragenoid, which is the binding subunit of cholera toxin, was studied in the rat L5 dorsal root ganglion. Sections were incubated with choleragenoid and treated immunocytochemically. Choleragenoid-like immunoreactive cells were then examined for possible co-localization with carbonic anhydrase-like, RT 97 (antibody to neurofilament proteins), substance P-like, somatostatin-like and calcitonin gene-related peptide-like immunoreactivity and fluoride-resistant acid phosphatase (FRAP) activity, using adjacent sections. A subpopulation of dorsal root ganglion neurons exhibited choleragenoid-like immunoreactivity. The majority of these were medium-sized and large neurons. The strongest immunoreactivity was found in the area of the plasma membrane, but strong reactivity was also seen in the cytoplasm. The majority of the choleragenoid-like immunoreactive cells showed carbonic anhydrase-like and RT 97 immunoreactivity. Cells showing co-localization of choleragenoid-like and neuropeptide-like immunoreactivity or activity for FRAP were rarely observed. Our results suggest that the GM1 receptor is localized primarily on carbonic anhydrase-containing and RT 97-immunoreactive primary sensory neurons.
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PMID:Immunocytochemical evidence for the localization of the GM1 ganglioside in carbonic anhydrase-containing and RT 97-immunoreactive rat primary sensory neurons. 249 5

The effect of the ganglioside GM1 on autotomy, a nociceptive behavioral marker for neuropathic pain, and substance P depletion was determined in a rat model of peripheral mononeuropathy, sciatic cryoneurolysis (SCN). SCN is produced by the application of a cryoprobe to the common sciatic nerve using a freeze-thaw-freeze cycle. Due to structural sparing of the nerve, regenerative processes are not precluded. After this peripheral nerve insult, behavioral and neurochemical changes occur that support the use of SCN as a neuropathic pain model. These changes include: autotomy with coincident transient weight loss and paling of eye color suggestive of increased sympathetic activity, spontaneous nociceptive behaviors, touch-evoked allodynia, prolonged mechanical allodynia, ipsilateral decrease of immunoreactive substance P, and increases in spinal cord dynorphin expression. Incidence and severity of autotomy were assessed after the intraperitoneal administration of GM1 (1, 10, and 20 mg/kg) or saline injected daily for 2 days before SCN, the day of surgery, and for 14 days after surgery. In a subset of two rats from each treatment group, transcardiac perfusion was performed and spinal cords were processed for substance P immunoreactivity. GM1 at 10 and 20 mg/kg doses significantly attenuated autotomy as compared with saline-treated rats (P = 0.007 and 0.0001, respectively). However, GM1, at the doses studied, failed to alter the spinal substance P depletion 21 days after SCN. These results indicate that the ganglioside GM1 may have a role in the clinical management of neuropathic pain after peripheral nerve injury.
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PMID:The ganglioside GM1 decreases autotomy but not substance P depletion in a peripheral mononeuropathy rat model. 769 Jan 98

This study investigated the status of substance P (SP), methionine-enkephalin (Met-Enk) and dynorphin A(1-13) (Dyn A) in the spinal cord of aged Sprague-Dawley rats and the effect of GM1 ganglioside on these neuropeptides. SP and Met-Enk, but not Dyn A, were decreased in both dorsal and ventral horns of the aged spinal cord. Treatment with GM1 ganglioside (30 mg/kg i.p., daily for 30 days) restored, in part, the neuropeptide deficits in the ventral horns, but not in the dorsal horns. This information might be important for understanding the sensory and motor deficits associated with ageing, and how the spinal cord neuropeptides might be amplified in the aged spinal cord.
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PMID:Decreased neuropeptide content in the spinal cord of aged rats: the effect of GM1 ganglioside. 1020 81

Biological substances with neurotrophic activities, such as nerve growth factor (NGF) and monosialoganglioside GM1, have been considered as agents for diabetic peripheral neuropathy. Because recent studies have suggested that decreased availability of these substances might contribute to the pathogenesis of diabetic peripheral neuropathy, some clinical trials of NGF for diabetic peripheral neuropathy have been conducted and have led to mixed conclusions. The major reasons were its limited delivery to the nervous system and adverse effects induced by subcutaneous injection, which was necessary because NGF is a polypeptide. The current study investigates whether an orally active sialic acid derivative, MCC-257, has neuroprotective properties in diabetic peripheral nerves. MCC-257 augmented NGF activity in cultured dorsal root ganglia and PC12 (pheochromocytoma 12) cells. Treatment with MCC-257 elevated NGF levels in the sciatic nerve, accompanied by improvement in nerve conduction velocity in streptozotocin-induced diabetic animals. More importantly, MCC-257 ameliorated small fiber dysfunctions, including thermal hypoalgesia, substance P content, and histopathological innervation in the plantar skin of diabetic animals. Thus, the orally active neurotrophin enhancer provides a new option for the clinical treatment of diabetic peripheral neuropathy.
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PMID:Orally active neurotrophin-enhancing agent protects against dysfunctions of the peripheral nerves in hyperglycemic animals. 1650 23

The neuropeptide-immunoreactive (IR) and neurofilament-IR neurons are two major phenotypical classes in dorsal root ganglion (DRG). Targets of neuronal innervation play a vital role in regulating the survival and differentiation of innervating neurotrophin-responsive neurons. Monosialoganglioside (GM1) has been considered to have a neurotrophic factor-like activity. Both GM1 and target skeletal muscle (SKM) cells are essential for the maintenance of the function of neurons. However, whether target SKM cells and GM1, alone or associated, generate neuropeptide or neurofilament expression remains unclear. The aim of the present study is to investigate the effects of GM1 or/and SKM on DRG neuronal phenotypes. DRG neurons containing the neuropeptide substance P (SP) and neurofilament 200 (NF-200) were quantified using immunofluorescent labeling in cultures of DRG, which was dissected out at times before (at embryonic days 12.5, E12.5) and after (at E19.5) sensory neurons contact peripheral targets in vivo. DRG neurons were cultured in absence or presence of GM1 or/and SKM cells. In this experiment, we found that: (1) GM1 promoted expression of SP and NF-200 in E12.5 DRG cultures; (2) SKM cells promoted expression of NF-200 but not SP in E12.5 DRG cultures; (3) GM1 and target SKM cells had additive effects on expression of SP and NF-200 in E12.5 DRG cultures; and (4) SKM or/and GM1 did not have effects on expression of SP and NF-200 in E19.5 DRG cultures. These results suggested that GM1 could influence DRG, two major neuronal phenotypes, before sensory neurons contact peripheral targets in vivo. Target SKM cells could only influence neurofilament-expressed neuronal phenotype before sensory neurons contact peripheral targets in vivo. GM1 and SKM cells had the additive effects on two major DRG neuronal classes, which express neuropeptide or neurofilament when DRG cells were harvested before sensory neurons contact peripheral targets in vivo. These results offered new clues for a better understanding of the association of GM1 or/and SKM with neuronal phenotypes.
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PMID:Co-administration of monosialoganglioside and skeletal muscle cells on dorsal root ganglion neuronal phenotypes in vitro. 1958 69

Substance P (SP) is one of the target neurotransmitters associated with diseases related to chronic inflammation, pain and depression. The selective receptor for SP, NK(1)R is located in the heterogeneous microdomains or caveolae in membrane. Gangliosides, specifically GM1, are markers of these heterogeneous sites. Also, gangliosides are considered as important regulatory elements in cell-cell recognition and cell signaling. In the present work, we describe the conformations of Substance P in the presence of ternary membrane systems containing GM1 at the physiological concentration. SP is mostly unstructured in water, but appears as extended 3(10) helical or turn III in isotropic bicelles, more pronounced in the presence of GM1. NMR results suggest that, in the GM1 containing bicelles, the peptide is more inserted into the membrane with its C-terminus, while N-terminus lies close to the membrane-water interface. The NMR-derived conformation of SP in GM1 bicelles is docked on homology modeled NK(1)R and resulting interactions satisfy reported mutagenesis, fluorescence, photo-affinity labeling and modeling data. The results highlight efficacy of GM1 in membrane in providing structure in an otherwise flexible neurotransmitter Substance P; thus providing indication that it may be useful also for other neurotransmitter peptides/proteins associated with membrane.
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PMID:NMR evidence of GM1-induced conformational change of Substance P using isotropic bicelles. 2093 48