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 production of substance P and the mRNA encoding its precursor (preprotachykinin, PPT) is regulated by nerve growth factor (NGF) in dorsal root ganglion (drg) neurons. To explore the mechanism by which NGF regulates the production of PPT mRNA, we have transfected PC12 cells and F11 cells with plasmids containing the bovine PPT promoter linked to the reporter gene chloramphenicol acetyltransferase (CAT). We have identified (i) functional elements within the PPT promoter which are necessary for expression in the absence of NGF and (ii) two separate regions, each of approximately 250 bp, which confer NGF responsiveness. Both regions contained a sequence element, similar to a known transcription factor binding site, which is present in several other NGF-regulated genes.
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PMID:Identification of nerve growth factor-responsive sequences within the 5' region of the bovine preprotachykinin gene. 174 55

A direct relationship exists between shear stress and endothelium-dependent NO-mediated vasodilation of blood vessels. The transduction of shear stress to the biochemical signals resulting in the production of NO is, however, unknown. We tested the hypothesis that integrin binding to Arg-Gly-Asp(RGD) peptide sequences in extracellular matrix proteins is a critical step in initiation of the signaling sequence whereby shear stress activates endothelial tyrosine kinase(s) and induces vasodilation of isolated arterioles. Isolated coronary arterioles were exposed to increasing shear stress under control conditions and in the presence of a synthetic peptide, GRGDNP, to competitively inhibit integrin binding to extracellular matrix proteins containing RGD peptide sequences. Intraluminal GRGDNP (0.1, 0.5, and 1.0 mmol/L) inhibited shear stress-induced vasodilation in a concentration-dependent manner. Application of GRGDNP had no effect on endothelium-dependent relaxation to substance P (10(-12) to 10(-8) mol/L). An inactive structural analogue, GRGESP, did not alter shear stress-induced vasodilation. To further elucidate the integrin involved in shear stress-induced vasodilation, we administered a blocking antibody to the integrin beta 3 chain (F11) and observed significant attenuation of the vasodilation. Shear stress was also associated with an increase in tyrosine kinase activity, as assessed by anti-phosphotyrosine binding. Application of GRGDNP significantly decreased anti-phosphotyrosine binding during shear stress, suggesting a link between tyrosine kinase activation and integrin signaling during this vasodilatory response. Taken together, these results indicate that integrin-matrix interactions, possibly at focal adhesions, are of cardinal importance in the signaling pathway of shear stress-induced vasodilation.
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PMID:Integrin signaling transduces shear stress--dependent vasodilation of coronary arterioles. 904 51

F11 cells are a dorsal root ganglion (DRG) cell line used to model the function of authentic type C, peptidergic, nociceptive neurons. The cellular events underlying the antinociceptive effects of (+/-)-epibatidine, a nicotinic acetylcholine receptor (nAChR) ligand that is 200-fold more potent than morphine, is unknown. The present study investigated the ability of cholinergic channel activators (ChCAs) to effect nAChR-gated ion flux and modulate the release of substance P (SP), a neuropeptide identified to play a critical role in nociception. The prototypical agonists (-)-nicotine and (-)-cytisine, the ganglionic stimulant 1,1-dimethyl-4-phenylpiperazinium, the novel ChCA ABT-418 [(S)-3-methyl-5-(-1-methyl-2-pyrrolidinyl)isoxazole], and (+/-)-epibatidine evoked a concentration-dependent stimulation of rubidium (86Rb+) efflux with EC50 values of 14.2 +/- 1.6, 63.4 +/- 24, 3.8 +/- 2.0, 29.8 +/- 2.6, and 0.019 +/- 0.001 microM as well as maximal intrinsic activities of 100, 97, 69, 75, and 102%, respectively. The noncompetitive nAChR antagonist mecamylamine potently antagonized (-)-nicotine-evoked ion flux, whereas the competitive antagonist dihydro-beta-erythroidine was a weak antagonist, giving support to an alpha3beta4 nAChR subtype. In addition, concentrations of (+/-)-epibatidine, similar to those necessary to induce maximal 86Rb+ efflux, evoked spontaneous release of SP from these cells, which was blocked by mecamylamine. Furthermore, prolonged exposure to (+/-)-epibatidine desensitized the functional response of the nAChR in this cell line (IC50 = 12 +/- 9 nM). These findings in F11 cells provide a model to investigate the role nAChRs play in modulating DRG cell function, and may lead to insights into the role these receptors have in modulating nociceptive transmission.
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PMID:Evidence for nicotinic receptors potentially modulating nociceptive transmission at the level of the primary sensory neuron: studies with F11 cells. 928 14

Recent evidence suggests a role of prepronociceptin/orphanin FQ (preproN/OFQ) derived neuropeptides in nociceptive signaling. Here, we examined the expression of preproN/OFQ and the nociceptin receptor ORL1 (opioid receptor like receptor 1) in the dorsal root ganglion (DRG) of the rat in relation to that of substance P (SP) and calcitonin gene-related peptide (CGRP). Double labeling in situ hybridization revealed a constitutive expression of preproN/OFQ in a distinct minor subpopulation of very small DRG neurons with no evidence for coexpression with either SP or CGRP. However, a major subpopulation of the preproN/OFQ-positive neurons showed direct juxtaposition to SP and CGRP containing neurons. ORL1 was abundantly expressed with a high degree of coexpression with SP (72%) and CGRP (82%) suggesting that N/OFQ may presynaptically modulate primary sensory nociceptive signaling. The DRG cell line F11 was found to express preproN/OFQ, but not ORL1, and, therefore, is well suited to study the mechanisms of N/OFQ gene regulation in vitro.
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PMID:Relationship of pronociceptin/orphanin FQ and the nociceptin receptor ORL1 with substance P and calcitonin gene-related peptide expression in dorsal root ganglion of the rat. 1293 25

The proinflammatory and lipopolysaccharide (LPS)-inducible cytokine tumor necrosis factor alpha (TNFalpha) has been shown to enhance primary sensory nociceptive signaling. However, the precise cellular sites of TNFalpha and TNF receptor synthesis are still a matter of controversy. Therefore, we differentiated the neuronal and non-neuronal sites of TNFalpha, TNFR1, and TNFR2 mRNA synthesis in dorsal root ganglion (DRG) of control rats and evaluated how their expression is altered under systemic challenge with LPS. In situ hybridization (ISH), RT-PCR analysis of laser-microdissected cells, and immunocytochemistry revealed absence of TNFalpha from DRG neurons and LPS-induced expression of TNFalpha exclusively in a subpopulation of non-neuronal DRG cells. Using RT-PCR and Northern blotting TNFR1 and TNFR2 mRNAs were found to be constitutively expressed and increased after LPS. TNFR1 mRNA was expressed in virtually all neurons and in non-neuronal cells with increased levels after LPS in both. TNFR2 was exclusively expressed and regulated in non-neuronal cells. RT-PCR analysis of microdissected DRG neurons and of the sensory neuronal cell line F11 confirmed the neuronal expression of TNFR1 and excluded that of TNFR2. Double ISH revealed varying levels of TNFR1 mRNA in virtually all DRG neurons including putative nociceptive neurons coding for calcitonin gene-related peptide, substance P, or vanilloid receptor 1. Taken together, we provide evidence that non-neuronally synthesized TNFalpha may directly act on primary afferent neurons via TNFR1 but not TNFR2. This is likely to be relevant under conditions of inflammatory pain and infections accompanied by widespread TNFalpha synthesis and release and may drive sickness behavior.
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PMID:Cell-specific expression and lipopolysaccharide-induced regulation of tumor necrosis factor alpha (TNFalpha) and TNF receptors in rat dorsal root ganglion. 1550 49