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 characteristics of the different populations of sensory nerve terminals that selectively contact pulmonary neuroepithelial bodies (NEBs) in rat lungs were investigated after chemical denervation with capsaicin and compared with control lungs. Vagal calbindin D28k and P2X(3) purinoceptor immunoreactive (IR) afferent nerve terminals contacting NEBs appeared to have their origin in the nodose ganglion. Thick CB/P2X(3)-IR nerve fibers were seen to be myelinated and to lose their myelin sheaths just before branching and protruding intraepithelially between the NEB cells. This vagal sensory component of the innervation of NEBs was not affected by capsaicin nor expressed capsaicin receptors (vanilloid receptor subtype 1). A second sensory nerve fiber population that selectively innervates pulmonary NEBs in the rat lung consists of thin unmyelinated nonvagal substance P/calcitonin gene-related peptide IR nerve fibers, contacting mainly the basal pole of pulmonary NEBs, and having their origin in dorsal root ganglia. In concordance with vanilloid receptor 1 expression on these nerve terminals, the spinal sensory substance P/calcitionin gene-related peptide-IR component of the innervation of NEBs was depleted by systemic capsaicin treatment. The complex sensory innervation pattern of pulmonary NEBs characterized in the present study strongly suggests that, physiologically, pulmonary NEBs represent a group of intraepithelial receptors that may be able to accommodate various local and central reflex actions, in relation to both chemo- and mechanosensory stimuli.
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PMID:Dual sensory innervation of pulmonary neuroepithelial bodies. 1259 50

Neurons in rat superficial dorsal horn that express neurokinin receptor 1 (NK1), a receptor for substance P, play a critical role in the development of hyperalgesia. Thermal hyperalgesia is dramatically reduced after ablation of these neurons, but, paradoxically, not in mice that lack the NK1 receptor (Mantyh et al. [1997] Science 278:275-279). Because primary afferents that express vanilloid receptor 1 (VR1), a receptor for noxious heat, are essential for thermal nociception and hyperalgesia, we reasoned that VR1-positive fibers may terminate onto NK1-expressing dorsal horn neurons. We therefore combined immunofluorescent staining for VR1 and NK1 to show that NK1-positive neurons in lamina I are contacted by VR1-positive fibers. That these contacts represent synapses was verified by staining for the presynaptic marker synaptophysin and by electron microscopy. By combining retrograde tracing with immunocytochemistry, we also found that most NK1-positive cells contacted by VR1-positive fibers project to the lateral parabrachial nucleus. Because quantitative evaluation suggests a preferential targeting of NK1-positive lamina I neurons by fibers containing VR1, these results demonstrate a significant monosynaptic innervation of spinoparabrachial neurons by VR1-positive afferents.
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PMID:VR1-positive primary afferents contact NK1-positive spinoparabrachial neurons. 1268 89

In the present study, the effect of intestinal schistosomiasis on the extrinsic sensory innervation of the murine ileum was investigated. Immunocytochemical techniques to localize calcitonin gene-related peptide (CGRP), substance P (SP), and vanilloid receptor 1 (VR1) were combined with retrograde tracing techniques and capsaicin treatment. Neurochemical characterization of extrinsic primary afferent neurons (EPANs) in normal and capsaicin-treated mice, revealed that CGRP and VR1, but not SP, were expressed in extrinsic afferents. Immunocytochemical analysis using the above-mentioned antibodies yielded three different populations of neurons in both dorsal root and nodose ganglia, namely CGRP/--, SP/--, and CGRP/SP-expressing neurons. Retrograde tracing revealed that only CGRP/--expressing neurons projected to the ileum. Intestinal schistosomiasis resulted in an upregulation of the number of CGRP-immunoreactive (ir) nerve fibers in the lamina propria of the villi, coinciding with an increase in mucosal mast cells in acutely and chronically infected animals. In infected animals, mucosal mast cells were found closely associated with a dense mucosal CGRP-ir fiber network. Neonatal capsaicin treatment led to a 70% reduction in the number of mucosal mast cells. In conclusion, the present study provides evidence that CGRP is a valid marker for EPANs in the mouse ileum, which are involved in the recruitment of mucosal mast cells. Morphological evidence is provided of a neuroimmune interaction between mucosal mast cells and EPANs in schistosoma-infected mice.
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PMID:Effect of intestinal inflammation on capsaicin-sensitive afferents in the ileum of Schistosoma mansoni-infected mice. 1276 86

Oncostatin M belongs to the interleukin-6 family of cytokines and acts as a multifunctional cytokine during murine embryogenesis and in inflammatory reactions. Although it has been demonstrated that oncostatin M has biological activities on many types of cells, including hepatocytes, dermal fibroblasts and endothelial cells, the roles of oncostatin M in the murine peripheral nervous system remain unclear. Here, we investigated the expression of specific beta-subunit of oncostatin M receptor in the dorsal root ganglia of adult mice. In the adult dorsal root ganglia, beta-subunit of oncostatin M receptor was exclusively expressed in small-sized neurons. Approximately 13% of total dorsal root ganglia neurons in mice contained beta-subunit of oncostatin M receptor. The double-immunofluorescence method revealed that approximately 28% of beta-subunit of oncostatin M receptor-positive neurons contained TrkA immunoreactivity, 63% expressed Ret immunoreactivity and 58% bound isolectin B4. No neuropeptides, including substance P and calcitonin gene-related peptide, were contained in the neurons. In addition, all beta-subunit of oncostatin M receptor-positive neurons expressed both vanilloid receptor 1 and P2X3 purinergic receptor. These neurons projected to the inner portion of lamina II in the dorsal horn of spinal cord and the dermis of skin. Seven days after sciatic nerve axotomy, the expression of beta-subunit of oncostatin M receptor was down-regulated in the lumbar dorsal root ganglia of the injured side. Our study demonstrated that beta-subunit of oncostatin M receptor was expressed in both cell bodies and processes of nonpeptidergic nociceptive neurons in adult mice, suggesting that oncostatin M may affect the nociceptive function of the neurons through the modulation of vanilloid receptor 1 and P2X3 expression.
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PMID:Expression of oncostatin M receptor beta in a specific subset of nociceptive sensory neurons. 1281 62

Substance P and neurokinin A (NKA) have potent pro-inflammatory effects in the airways. The release of these neuropeptides from primary afferent (sensory) nerve endings to various stimuli is considered to be induced by activation of the capsaicin (vanilloid) receptor (VR1). In this study, retrograde neuronal tracing studies were combined with immunohistochemistry for VR1 and substance P to investigate the occurrence and distribution of substance P and VR1 receptor expression in mouse trigeminal neurons that were identified by retrograde labeling with Fast blue dye from the nasal mucosa. Fast blue signaling was observed in mucosa layers of the right nasal cavity and in sensory trigeminal neurons close to the division of the ophthalmic and maxillary nerve. Expression patterns of VR1 and substance P were found with different frequencies: 11.3+/-1.2% (mean+/-SEM) were immunoreactive for VR1, 4.9+/-1.1% for VR1 and SP, and 6.4+/-1.3% only for VR1 but not for SP. These VR1-positive neurons were partly binding to lectin I-B4, indicating VR1-expression in non-peptidergic upper airway C-fibers. In conclusion, based on the extent of SP and VR1 co-localization in nasal afferent neurons, the present study suggests that, following a peripheral activation of the VR1 receptor on SP afferents, there could be a triggering of SP-mediated phenomena, including those related to inflammation, such as plasma extravasation.
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PMID:Expression of substance P and vanilloid receptor (VR1) in trigeminal sensory neurons projecting to the mouse nasal mucosa. 1290 43

The vanilloid receptor VR1 renders a group of primary afferents that express it sensitive to noxious heat and capsaicin, and is thus an important marker for nociceptors. We use double immunofluorescence and confocal microscopy to show that the density of VR1-positive fibers and boutons in the dorsal horn increases progressively from spinal segments L4 to L6 and that the colocalization of VR1 with the neuropeptide substance P (SP) in lamina I and along the lateral collateral path, where the majority of visceral afferents terminate, is negligible at L4, but substantial at L6. We conclude that VR1 is expressed by visceral afferents to the lower lumbar spinal cord in the rat, which also express SP.
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PMID:Vanilloid receptor VR1-positive afferents are distributed differently at different levels of the rat lumbar spinal cord. 1294 82

A capsaicin-like endogenous ligand of vanilloid (VR1) receptors, N-arachidonoyl-dopamine, was recently identified in bovine and rat nervous tissue, and found to be almost as potent as capsaicin, and 5-10-fold more potent than anandamide, on these receptors, both in isolated cells and in vivo. Here we have investigated if N-arachidonoyl-dopamine also exerts other capsaicin-like effects at VR1 receptors in some isolated organ preparations. N-arachidonoyl-dopamine exerted a potent contractile response of guinea pig isolated bronchi (EC50=12.6 +/- 1.7 microM, Emax=69.2 +/- 2.4% of carbachol Emax), which was blocked by pre-treatment with capsaicin or with the VR1 antagonist capsazepine, as well as by a combination of tachykinin NK1 and NK2 receptor antagonists. In this assay, N-arachidonoyl-dopamine was less and more potent and/or efficacious than capsaicin (EC50=40.0 nM; Emax=93.5%) and anandamide (EC50=15.2 microM, Emax=38.0%), respectively. Unlike capsaicin and anandamide, forskolin or ethanol did not enhance N-arachidonoyl-dopamine effect in this preparation, whereas epithelial denudation resulted in a 2.5-fold increase in potency without affecting the efficacy. N-arachidonoyl-dopamine also contracted the isolated guinea pig urinary bladder, although in this preparation, as well as in the isolated rat urinary bladder, the potency (EC50=3.7 +/- 0.3 and 19.9 +/- 0.1 microM) and/or efficacy (Emax=12.0 +/- 0.1% and 20.7 +/- 0.7% of carbachol Emax) of the compound were significantly lower than those of both capsaicin and anandamide. These data suggest that the extent to which exogenous N-arachidonoyl-dopamine activates VR1 receptor in isolated organs is largely dependent on pharmacodynamics and bioavailability.
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PMID:Capsaicin-like effects of N-arachidonoyl-dopamine in the isolated guinea pig bronchi and urinary bladder. 1295 66

Dorsal horn neurons expressing receptor for substance P (SP), the neurokinin 1 (NK1) receptor, play an important role in transmission and processing of nociceptive stimuli. To identify and study these neurons in the rat spinal cord slice preparation, we used fluorescence-conjugated SP to label NK1 receptor-expressing neurons. Labeled neurons in lamina I and III/IV were patch clamped and the vanilloid receptor 1 (TRPV1) agonist, capsaicin, was applied to evoke glutamate release from central terminals of peripheral nociceptors. Capsaicin induced an increase in the frequency of miniature excitatory postsynaptic currents in 73% of lamina I and 43% of lamina III/IV neurons expressing NK1-receptor indicating that these neurons receive direct input from capsaicin and heat sensitive nociceptors.
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PMID:Neurokinin receptor 1-expressing spinal cord neurons in lamina I and III/IV of postnatal rats receive inputs from capsaicin sensitive fibers. 1462 38

Previously, we reported that the injection of capsaicin into the lateral cerebroventricle (i.c.v.) stimulated gastric acid secretion via vanilloid VR1 receptors and the vagal cholinergic pathways in anesthetized rats. In the present study, we investigated the involvement of receptor systems for neurokinin A, calcitonin gene-related peptide (CGRP) and glutamate in the vanilloid VR1 receptor-mediated response. The i.c.v. injection of neurokinin A (30 nmol) stimulated gastric acid secretion in the presence of cis-2-(diphenylmethyl)-N-[(2-iodophenyl)methyl]-1-azabicyclo[2.2.2]octan-3-amine oxalate (L-703606, a tachykinin NK1 receptor antagonist, 30 nmol) and the effect was inhibited by cyclo[Gln-Trp-Phe-Gly-Leu-Met] (L-659877, a tachykinin NK2 receptor antagonist, 30 nmol); the values were 145.9 +/- 32.3 and 21.1 +/- 16.6 microEq HCl per 120 min, respectively. The value in the control group was 14.3 +/- 3.8 microEq HCl. The tachykinin NK2 receptor-mediated secretion was inhibited by i.c.v. injections of antagonists of the CGRP1 receptor (human CGRP fragment 8-37, 15 nmol) and non-N-methyl-D-aspartate (non-NMDA)-type glutamate receptor (6-cyano-7-nitroquinoxaline-2,3-dione, 10.9 nmol); the values were 30.8+/-29.8 and 5.7+/-16.9 microEq HCl, respectively. Gastric acid secretion induced by the i.c.v. injection of 30 nmol capsaicin (178.4 +/- 34.0 microEq HCl) was inhibited by antagonists of tachykinin NK2 (23.7 +/- 6.2) and CGRP1 (21.2 +/- 8.5), but not tachykinin NK1 (181.4 +/- 37.0), receptors. The gastric acid secretion induced by capsaicin was decreased by the i.c.v. pre-injection of low doses of neurokinin A or CGRP, which alone had no effect on the secretion. These findings suggest the involvement of tachykinin NK2, CGRP and non-NMDA receptor systems in the vanilloid VR1 receptor-mediated regulation of gastric acid secretion in the rat brain regions close to the lateral cerebroventricle.
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PMID:Role of neuropeptide receptor systems in vanilloid VR1 receptor-mediated gastric acid secretion in rat brain. 1498 54

Evidence suggests that capsaicin-sensitive substance P (SP)-containing trigeminal ganglion neurons innervate the spiral modiolar artery (SMA), radiating arterioles, and the stria vascularis of the cochlea. Antidromic electrical or chemical stimulation of trigeminal sensory nerves results in neurogenic plasma extravasation in inner ear tissues. The primary aim of this study was to reveal the possible morphological basis of cochlear vascular changes mediated by capsaicin-sensitive sensory nerves. Therefore, the distribution of SP and capsaicin receptor (transient receptor potential vanilloid type 1-TRPV1) was investigated by double immunolabeling to demonstrate the anatomical relationships between the cochlear and vertebro-basilar blood vessels and the trigeminal sensory fiber system. Extensive TRPV1 and SP expression and co-localization were observed in axons within the adventitial layer of the basilar artery, the anterior inferior cerebellar artery, the SMA, and the radiating arterioles of the cochlea. There appears to be a functional relationship between the trigeminal ganglion and the cochlear blood vessels since electrical stimulation of the trigeminal ganglion induced significant plasma extravasation from the SMA and the radiating arterioles. The findings suggest that stimulation of paravascular afferent nerves may result in permeability changes in the basilar and cochlear vascular bed and may contribute to the mechanisms of vertebro-basilar type of headache through the release of SP and stimulation of TPVR1, respectively. We propose that vertigo, tinnitus, and hearing deficits associated with migraine may arise from perturbations of capsaicin-sensitive trigeminal sensory ganglion neurons projecting to the cochlea.
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PMID:Co-localization of the vanilloid capsaicin receptor and substance P in sensory nerve fibers innervating cochlear and vertebro-basilar arteries. 1502 32


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