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)

The response of sensory nerve fibres to inflammation in young adult rat molars has recently been shown to include increases in nerve sprouting and neuropeptide content. The objective was to evaluate neural responses to class V dental preparations in molars of old (1-2 yr) as compared with young adult rats (3-4 months). Tissues were investigated immunocytochemically 4 days post-injury for the sensory neuropeptides calcitonin gene-related peptide (CGRP) and substance P. Quantitative image analysis of the material demonstrated that more immunoreactivity was present for CGRP than for substance P in intact control teeth for each age group. Four days after injury, both immunoreactivities were increased in pulp adjacent to the injury in both young and old teeth. The increase depended on at least three factors: (1) enhanced immunoreactivity of the nerve fibres; (2) increased terminal nerve sprouts near the injury and (3) elevated peptide content of the pulp tissue. Although the incidence of CGRP- and substance P-immunoreactive nerve fibres had decreased in older teeth, the proportional increases in both neuropeptides near the injury were greater in old than in young teeth, owing to a reduction in pulpal volume during ageing. Pulpal tissue was also immunostained for the low-affinity nerve growth factor receptor (p75-NGFR) as an index of pulpal ageing; and an extensive decrease was found in the old adult as compared to young adult rats. These results indicate that old rats maintain the capacity for nerve sprouting despite the decreases in p75-NGFR labelling of pulp cells, pulp volume and nerve fibre numbers that occur as part of dental ageing.
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PMID:Effect of ageing on responses of nerve fibres to pulpal inflammation in rat molars analysed by quantitative immunocytochemistry. 128 28

The growth-associated protein 43 (GAP43) is a neuronal membrane protein involved in axonal growth and regeneration as well as in the modulation of synaptic plasticity. It is present in sensory and sympathetic neurons, where it is consistently associated with the expression of nerve growth factor receptor (NGFr). We investigated, by means of immunohistochemistry, the presence and distribution of the GAP43-immunoreactivity (IR) and of the NGFr-IR in the adult normal human skin from various body regions. In adjacent sections, a comparison with the distribution of the neuronal markers protein gene product 9.5 (PGP 9.5), substance P (SP), and calcitonin gene-related peptide (CGRP) was performed. Our results indicate that in adult human skin 1) a GAP43-IR is morphologically present in epidermal and dermal nerve fibers; 2) a NGFr-IR is associated with neuronal as well as non-neuronal elements of cutaneous nerves; 3) the basal epidermal cell layer expresses a NGFr-IR, which is unevenly distributed according to the different body areas; and 4) there is suggestive evidence for a simultaneous expression of GAP43-, NGFr-, PGP 9.5-, SP-, and CGRP-IR in at least part of the cutaneous nerve fibers. The presence of GAP43-immunoreactive nerve fibers might be a marker of a continuous synaptic remodeling in adult skin, whereas the distribution of the NGFr-IR could be relevant for our understanding of the maintenance of the neuronal-target relationship(s).
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PMID:Expression of growth-associated protein 43 and nerve growth factor receptor in human skin: a comparative immunohistochemical investigation. 128 63

Aging of cat tooth pulp nerves involves ultrastructural changes, and changes in the expression of some neuropeptides and in the expression of the receptor for nerve growth factor. Electron microscopy of old pulps demonstrates loss and degeneration of unmyelinated and myelinated axons, as well as demyelination. Immunohistochemical findings show a marked age-related decrease in pulpal calcitonin-gene related peptide- and substance P-like immunoreactivity, and a reduction in nerve growth factor receptor-like immunoreactivity. Changes in neuropeptide expression are not entirely due to loss of nerve fibers, since most aging pulps contain nerve growth factor receptor-positive fibers which lack neuropeptide-like immunoreactivity. The changes reported here parallel the observation that there is an age-related reduction in sensitivity to pulpal stimulation, but may also contribute to the development of oral sensory phenomena such as neuropathic pain. Moreover, the senescent transformation of pulpal nerves probably affects hemoregulation of the pulp, and may thus have consequences for pulpal extraneuronal tissue.
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PMID:Changes in pulpal nerves with aging. 132 1

A monoclonal antibody raised against the human nerve growth factor receptor (NGFr) was used to map the distribution of NGFr-immunoreactivity (IR) in the trigeminal nuclear complex of 8- to 10-week-old, immature felines. Somata and fibers show NGFr-IR within the trigeminal ganglion and the mesencephalic trigeminal nucleus. NGFr-IR is also found in fibers within the trigeminal root entry zone, the spinal trigeminal tract, and in fibers and terminals within all the central trigeminal sensory nuclei. The NGFr-IR found within the trigeminal sensory nuclei typically occurs in circumscribed zones that vary in position for the different subnuclei. NGFr-IR is found in the dorsomedial and ventrolateral subdivisions of the main sensory nucleus, in the dorsomedial and occasionally in ventral positions within pars oralis, in dorsal and ventral regions within pars interpolaris, and primarily in outer lamina II with fibers that project to lamina V within pars caudalis/medullary dorsal horn. These results show some overlap with the central distribution of trigeminal primary afferent nociceptive fibers such as those found from the tooth pulp and overlap with the central distribution of such peptides as calcitonin gene-related peptide and substance P, but NGFr-IR is more restricted. Thus, it appears that NGFr-IR is associated with the endings of primary afferent fibers in the brain stem, and that these fibers may represent a certain subclass of primary afferent nociceptors. It is speculated that fibers showing NGFr-IR may have the ability to alter their response to peripheral deafferentation when compared to fibers lacking NGFr-IR.
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PMID:Localization of nerve growth factor receptor immunoreactivity in the trigeminal nucleus of kittens. 164 14

The distribution of nerve growth factor receptor (NGF receptor)-like immunoreactivity in pulps of developing primary and mature permanent cat canine teeth was examined, by use of a monoclonal antibody against NGF receptor detected by fluorescence immunohistochemistry and pre-embedding immunocytochemical light- and electron microscopy. Both primary and permanent pulps contained a vast number of NGF receptor-like immunoreactive nerves. Immunolabelling appeared to be localized both to axons and Schwann cells. In addition, many blood vessel walls in immature primary tooth pulps showed NGF receptor-like immunoreactivity, in contrast to permanent pulps where blood vessels rarely were NGF receptor-immunoreactive. Double-labelling immunofluorescence experiments revealed that in the permanent pulp a majority of the NGF receptor-positive nerves also showed calcitonin gene-related peptide (CGRP)-like immunoreactivity, and many showed substance P-like immunoreactivity. However, nerve fibers with neuropeptide Y-like immunoreactivity lacked NGF receptor-like immunoreactivity. In developing primary tooth pulps fewer NGF receptor-positive nerves were CGRP-like immunoreactive or substance P-like immunoreactive, as compared to the permanent pulp. Neuropeptide Y-like immunoreactive nerve fibers were not detected in the primary tooth pulp. The results suggest a role for nerve growth factor in both developing and mature sensory nerves of the tooth pulp.
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PMID:Nerve growth factor receptor-like immunoreactivity in primary and permanent canine tooth pulps of the cat. 165 63

Substance P immunoreactivity is localized in discrete subsets of neurons in the human cerebral cortex and basal ganglia. In the normal human cerebral cortex, a subset of aspiny local circuit neurons in deep cortical layers and the cortical subplate contain preprotachykinin mRNA and substance P immunoreactive. These neurons, which contain NADPH diaphorase (NO synthase) activity, are strikingly depleted in Alzheimer's disease--in contrast to other local circuit neurons--suggesting that they may be an early target of the degenerative process. In the human basal ganglia, substance P immunoreactivity and mRNA are localized in a subset of spiny striatal neurons that project to the internal segment of the globus pallidus. These neurons are enriched in D1 dopamine receptors and dynorphin, and are calbindin and DARP 32 immunoreactive. A separate subset of aspiny striatal local circuit neurons also contain substance P immunoreactivity. Fiber and terminal staining is prominent in the matrix compartment of the ventromedial striatum and persists dorsally as a rim outlining patches that contain lesser amounts of immunoreactivity. Intense fiber and terminal staining is found in the pars reticulata of the substantia nigra. In Huntington's disease, substance P is depleted in the striatum in parallel with the dorsoventral gradient of neuronal loss. Terminal staining is progressively depleted in the pallidum and substantia nigra in tandem with striatal atrophy. Substance P receptor immunoreactivity, defined with two polyclonal antisera raised against synthetic peptides derived from the substance P receptor sequence, intensely labels a subset of large neurons in the nucleus basalis and striatum identical to neurons labeled with choline acetyltransferase and nerve growth factor receptor antibodies (although striatal cholinergic neurons do not contain nerve growth factor receptor immunoreactivity in the human). These cholinergic neurons resist degeneration in Huntington's disease but are sensitive to degeneration in Alzheimer's disease. Less intensely labeled neurons include pyramidal neurons in the hippocampal CA2 field, nonpyramidal neurons in CA1-4, pyramidal and nonpyramidal neurons in deep neocortical layers and in the cortical subplate. Substance P receptor immunoreactivity is not well defined in the human globus pallidus or substantia nigra.
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PMID:Substance P and substance P receptor histochemistry in human neurodegenerative diseases. 769 86

Injury to the sciatic nerve leads to the transganglionic degeneration of sensory axons and to the induction of neurotrophins and p75 nerve growth factor receptor synthesis by the denervated Schwann cells. Sciatic nerve axotomy caused a marked loss of substance P and of met-enkephalin in the lumbar cord. Substance P immunostaining and pre-proenkephalin mRNA expression were reduced in the dorsal horn layers I and II ipsilaterally to the lesion. Treating rats with low doses (0.25 mg/kg) of heparin or COS 8, a natural glycosaminoglycan mixture with low anticoagulant activity, the peptide loss was prevented and the content increased of about 50% above control values. The effects of COS 8 treatment were also evident on Schwann cells. COS 8 augmented the increase of nerve growth factor, brain-derived neurotrophic factor, and NT-3 mRNA expression in the distal stump of the axotomized sciatic nerve. Therefore, it can be concluded that glycosaminoglycans neuroprotective effects on lesioned sensory axons might have been mediated by the dramatic promotion of neurotrophin synthesis. Although the in vitro studies (Lesma et al.: J Neurosci Res, 1996) suggested also a likely direct effect as extracellular matrix components that is not mediated by trophic factors.
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PMID:Glycosaminoglycans in nerve injury: II. Effects on transganglionic degeneration and on the expression of neurotrophic factors. 895 69

In this study, enteric nervous system (ENS) of the fetal intestinal grafts was examined histopathologically. Forty-four rat fetal small intestines were transplanted syngenetically into the subcutaneous region of adult rats without vascular anastomosis. Thirty-two grafts survived. They were removed 2, 4, 6, and 8 weeks after transplantation and examined using (1) H&E staining, (2) AChE and NADPH-diaphorase histochemistry, and (3) protein gene product 9.5, S-100 protein, glial fibrillary acidic protein, tyrosine hydroxylase, nerve growth factor receptor, calcitonin gene-related peptide, neuropeptide Y, vasoactive intestinal peptide, somatostatin, and substance P immunohistochemistry. The grafts were compared with the intestines of 2-, 4-, 6- and 8-week-old control rats. ENS of the grafts was different from the controls as follows: (1) tyrosine hydroxylase and neuropeptide Y were markedly reduced but present, suggesting that the extrinsic innervation was present; (2) nitric oxide-producing neurons were well preserved in grafts; (3) hyperganglionosis in the myenteric plexus was seen in 6- and 8-week grafts; (4) AChE activity was increased in the circular muscle and in the lamina propria, (5) S-100 was increased in the lamina propria in 6- and 8-week grafts, (6) calcitonin gene-related peptide was increased in 6- and 8-week grafts, (7) nerve fibers in the muscle layers ran irregularly and disorderly, and (8) hypertrophy of smooth muscle layers. Our data show that although extrinsic as well as intrinsic innervation is present in the fetal intestinal grafts, there is hyperinnervation of the intrinsic nervous system and reduced innervation of the extrinsic ENS. These morphological changes in the ENS of the fetal intestinal grafts may result in motility dysfunction.
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PMID:Morphological changes in the enteric nervous system of the transplanted fetal rat intestine. 920 96

The type of trigeminal ganglion cells that express 5-HT1B receptors has not been well characterized, despite the fact that these receptors are important targets for anti-migraine drugs. We have therefore used combined in situ hybridization and immunofluorescence to examine the expression of 5-HT1B receptor messenger RNA in identified subpopulations of rat trigeminal ganglion cells. 5-HT1B-expressing cells accounted for 15% of all trigeminal ganglion cells, were medium sized, and showed immunoreactivity for either 200,000 mol. wt neurofilament, calcitonin gene-related peptide, or nerve growth factor receptor (trkA). In contrast few 5-HT1B cells showed immunoreactivity for substance P or binding of the lectin Griffonia simplicifolia IB4. Our results are consistent with 5-HT1B receptors acting to control the release of calcitonin gene-related peptide from trigeminal neurons with finely myelinated axons. 5-HT1B receptor agonists may reduce neurogenic vasodilation by activating such receptors. However many nociceptive trigeminal neurons, including the substance P and IB4-binding populations, do not express the 5-HT1B receptor.
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PMID:Expression of the 5-HT1B receptor by subtypes of rat trigeminal ganglion cells. 1065 26

1,6-Hexamethylene diisocyanate biuret trimer (HDI-BT) is a nonvolatile isocyanate that is a component of polyurethane spray paints. HDI-BT is a potent irritant that when inhaled stimulates sensory nerves of the respiratory tract. The role of sensory nerves in modulating lung injury following inhalation of HDI-BT was assessed in genetically manipulated mice with altered innervation of the lung. Knockout mice with a mutation in the low-affinity nerve growth factor receptor (NGFR), which have decreased innervation by nociceptive nerve fibers, and transgenic mice expressing nerve growth factor (NGF) from the lung-specific Clara cell secretory protein (CCSP) promoter, which have increased innervation of the airways, were exposed to HDI-BT aerosol and evaluated at various times after exposure. NGFR knockout mice exhibited significantly more, and CCSP-NGF transgenic mice exhibited significantly less injury and inflammation compared with wild-type mice, indicative of a protective effect of nociceptive nerves on the lung following HDI-BT inhalation. Transgenic mice overexpressing the tachykinin 1 receptor (Tacr1) in lung epithelial cells also showed less severe injury and inflammation compared with wild-type mice after HDI-BT exposure, establishing a role for released tachykinins acting through Tacr1 in mediating at least part of the protective effect. Treatment of lung fragments from Tacr1 transgenic mice with the Tacr1 ligand substance P resulted in increased cAMP accumulation, suggesting this compound as a possible signaling mediator of protective effects on the lung following nociceptive nerve stimulation. The results indicate that sensory nerves acting through Tacr1 can exert protective or anti-inflammatory effects in the lung following isocyanate exposure.
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PMID:Neuronal modulation of lung injury induced by polymeric hexamethylene diisocyanate in mice. 1767 70


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