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)

Periodontal disease is a common multifactorial chronic inflammatory disease in humans. In inflammatory conditions that are known to be associated with changes in nociception, such as arthritis, the neuronal expression of the proinflammatory neuropeptides, substance P and calcitonin gene-related peptide is altered. In this study the expression of these neuropeptides' mRNAs has been studied in an inflammatory model that shows no behavioural evidence of altered nociception. Periodontitis was induced in male rats by intragingival injection of lipopolysaccharide adjacent to the second right mandibular molar. The animals were killed at various times after lipopolysaccharide injection and right and left trigeminal ganglia and brain were processed for in situ hybridization for beta-preprotachykinin and alpha-calcitonin gene-related peptide mRNAs. Expression of both neuropeptide mRNAs was significantly increased only in small neurons in the mandibular division of the trigeminal ganglion ipsilateral to the LPS injection from 3 to 10 days postinjection. Neuropeptide mRNA expression was also significantly increased in the contralateral trigeminal ganglion at day 10. No significant changes in neuropeptide mRNA levels were seen in the maxillary and ophthalmic divisions of the trigeminal ganglia or in the trigeminal mesencephalic nucleus. The up-regulation of substance P and CGRP mRNAs in periodontal disease suggests that this is associated with the inflammatory process rather than nociception, as this disease does not appear to result in altered nociception in either rats or humans. The contralateral alteration in neuropeptide mRNA expression suggests a role for neurogenic mechanisms in the development of periodontal disease.
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PMID:Sensory neuropeptide mRNA up-regulation is bilateral in periodontitis in the rat: a possible neurogenic component to symmetrical periodontal disease. 1498 15

Dental pulp reactivity to various pro-inflammatory stimuli was independently evaluated in rats in terms of a vascular permeability increase and leukocyte recruitment. Substance P, calcitonin-gene related peptide (CGRP) and prostaglandin E(2) (in the picomol range) were applied to the exposed pulp from anesthetised animals and the plasma extravasation measured by the Evans blue content in the tissue following 10 min of administration. Leukocyte recruitment was evaluated morphometrically by counting the cell number present in serial sections of 1:3 4 microm pulp tissue 6 h after bacterial endotoxin (LPS; 0.06-1.2 microg/site) administration. Increase in pulp vascular permeability and cellular recruitment due to the injection of mentioned mediators in the skin or LPS in the peritoneal cavity were used as positive controls. Increase in vascular permeability in the pulp occurred in the same dose-range as observed in the skin, being CGRP the most active substance in both cases. However, it was necessary a higher dose of LPS (1.2 microg) to induce a similar cell recruitment in the pulp as that observed in the rat peritoneal cavity (0.3 microg). These data indicate that dental pulp reactivity presents the same pattern of increase in vascular permeability to other tissues in the rat, being CGRP the most potent mediator in this respect. In addition, they suggest the presence of CGRP receptors in the dental pulp. However, an adequate leukocyte recruitment response to bacterial endotoxin was not mounted, suggesting a deficiency in adhesion molecules in blood vessels in the rat dental pulp.
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PMID:Vascular and cellular responses to pro-inflammatory stimuli in rat dental pulp. 1509 1

1. Several observations suggest that tachykinins are involved in the pathogenesis of bronchopulmonary alterations. We have investigated the effect of antagonists for tachykinin NK1 (SR 140333), NK2 (SR 48968) or NK3 (SR 142801) receptors on inflammatory cell recruitment, tumour necrosis factor (TNF)-alpha and interleukin (IL)-6 release and matrix metalloproteinase (MMP)-9 activity in the bronchoalveolar lavage fluid (BALF) of mice exposed to lipopolysaccharide (LPS; 100 microg/mL aerosol for 30 min). 2. Treatment of mice with a combination of SR 140333 and SR 48968 (10(-6) mol/L, aerosol) significantly reduced the increase in the number of total cells and neutrophils and MMP-9 activity in the BALF of mice 2.5 h after LPS exposure. Treatment with the NK3 antagonist SR 142801 (10(-6) mol/L, aerosol) did not inhibit the influx of neutrophils, but markedly reduced the increase in TNF-alpha and IL-6 levels at 2.5 h and MMP-9 activity at 20 h. 3. These results show that the three tachykinin receptor antagonists may interfere with the development of airway inflammation, namely neutrophilia, TNF-alpha release or MMP-9 activity in the BALF of mice exposed to LPS and suggest that not only NK1 and NK2 receptors, but also NK3 receptors are involved in the modulation of the inflammatory response and airway remodelling.
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PMID:Interactions of tachykinin receptor antagonists with lipopolysaccharide-induced airway inflammation in mice. 1547 72

Substance P is elevated in plasma and in other tissues during Mg-deficiency, and was found localised to neuronal C-fibres of cardiac and intestinal tissues, where it could promote neurogenic inflammation. Plasma prostaglandin E2 (PGE2), indicative of systemic inflammation, rose significantly (>or=4 fold, p<0.01) after 1 week and remained elevated through week 2 and 3 in rat on the Mg-deficient (MgD) diet. Concomitantly, total blood glutathione decreased by 50%. Immunohistochemical staining for endotoxin (lipopolysaccaride, LPS) receptor, CD14 was prominent in macrophage-type cells in intestinal tissue; more importantly, cardiac tissue revealed both CD11b (monocyte/macrophage surface protein) and CD14 positive cells after 3 weeks in rats on MgD diet. Western blot analysis indicated a significant increase in the endotoxin receptor protein level in the 3 week MgD hearts. Since CD14 is known to be up-regulated in cells exposed to LPS, these observations suggest that prolonged Mg-deficiency results in increased intestinal permeability to bacterial products that induce the endotoxin receptor in cells localized to myocardial and intestinal tissues. These CD14 positive cells may amplify the cardiomyopathic inflammatory process by stimulating TNF-alpha and other pro-inflammatory cytokines.
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PMID:Intestinal and cardiac inflammatory response shows enhanced endotoxin receptor (CD14) expression in magnesium deficiency. 1618 88

This study assesses the effects of compound velutinol A obtained from M. velutina in the rat paw edema induced by several phlogistic agents. Attempts were made to analyze how velutinol A is able to inhibit kinin B(1) receptor-mediated inflammatory responses. Velutinol A (100 nmol/paw) partially reduced (about 30%) the edema evoked by carrageenan (300 microg/paw). However, velutinol A (100 nmol/paw) failed to affect the edema induced by histamine (200 nmol/paw), substance P (30 nmol/paw), PAF (10 nmol/paw) or BK (3 nmol/paw). Interestingly, the edema caused by the selective kinin B(1) receptor agonist des-Arg(9)-BK (100 nmol/paw) in animals pre-treated with PAF or LPS was significantly inhibited by velutinol A (100 nmol/paw) (48 and 46%, respectively). A similar inhibition of des-Arg(9)-BK-induced edema after pre-treatment with PAF was obtained with the non-peptidic and selective B(1) receptor antagonist SSR 240612 (60 nmol/paw) (46%). In addition, the systemic administration of velutinol A (10 mg/kg, i.p.) or SSR 240612 (1 mg/kg, i.p.) also caused a significant reduction of des-Arg(9)-BK (100 nmol/paw)-induced edema in PAF-treated rats (51 and 43%, respectively). The results provide convincing evidence that velutinol A selectively blocks the edema responses mediated by B(1) receptor activation in vivo. This compound might represent a new non-peptidic and selective antagonist for kinin B(1) receptors.
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PMID:Anti-edematogenic effects of velutinol A isolated from Mandevilla velutina: evidence for a selective inhibition of kinin B1 receptor-mediated responses. 1676 51

Endotoxemia is a life-threatening, inflammatory condition that involves multiple organ injury and dysfunction. Preprotachykinin-A (PPT-A) gene products, substance P (SP), and neurokinin-A have been shown to play an important role in neurogenic inflammation. To investigate the role of PPT-A gene products on multiple organ injury in LPS-induced endotoxemia, endotoxemia was induced by LPS administration (10 mg/kg, i.p.) in PPT-A gene-deficient mice (PPTA(-/-)) and the wild-type (WT) control mice (PPT-A+/+). I.p. administration of LPS to WT mice caused a significant increase in circulating levels of SP as well as in liver, lung, and kidney. PPT-A gene deletion significantly protected against liver, pulmonary, and renal injury following LPS-induced endotoxemia, as evidenced by tissue myeloperoxidase activities, plasma alanine aminotransferase, aspartate aminotransferase levels, and histological examination. Furthermore, PPT-A(-/-) mice had significantly attenuated chemokines, proinflammatory cytokines, and adhesion molecule levels in the liver, lung, and kidney. These results show that PPT-A gene products are critical proinflammatory mediators in endotoxemia and the associated multiple organ injury. In addition, the data suggest that deletion of the PPT-A gene protected mice against organ damage in endotoxemia by disruption in neutrophil recruitment.
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PMID:Role of preprotachykinin-A gene products on multiple organ injury in LPS-induced endotoxemia. 1799 2

We investigated effects of acetaminophen on LPS-induced hyperalgesia in various pain models. We examined the changes of pain behaviors induced by formalin injected subcutaneously (s.c.) in the hind paw, with substance P (SP) and glutamate injected inthrathecally (i.t.). Hyperalgesia was induced by LPS intraperitoneal injection 1 day prior to the pain test. LPS-induced hyperalgesia was exhibited in nociceptive behaviors induced by formalin s.c. (only in the second phase), SP and glutamate i.t. injection. APAP showed a dose-dependent antinociceptive effect on the saline- and LPS-pretreated group in the formalin and SP pain model. However, the analgesic effect of APAP was not observed in the glutamate pain model. To clarify the action site, APAP was administered i.t. or intracerebroventricularly (i.c.v.) 30 min prior to behavioral tests. The 2nd phase of formalin response was not only increased by LPS, but it also significantly attenuated by i.c.v. injections of APAP. However, the effect of APAP was observed only in the LPS-pretreatment, but not in the control group. These results suggest that LPS-induced hyperalgesia in the formalin 2nd phase may be involved in the SP-sensitive neuronal pathways, in which the hyperalgesic response elicited by LPS attenuated by APAP with supraspinal pain modulatory mechanisms.
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PMID:The differential effects of acetaminophen on lipopolysaccharide induced hyperalgesia in various mouse pain models. 1863 80

The sensory neuropeptides secretoneurin (SN) and substance P (SP) are involved in "neurogenic" inflammatory processes as they occur in bronchial asthma or allergic rhinitis. A possible interaction with basophils has not been reported to date. Basophils were isolated from healthy donors by magnetic cell sorting technique and migration was explored using Boyden microchemotaxis chambers. SN [10(-8)M] and SP [10(-6) to 10(-8)M] proved to be chemoattractants equally potent to FMLP [10(-8)M] or LPS [10 pg/ml]. Specific anti-SN antibodies and a trypsinization preparation of SN were used to determine the specificity of the SN effect on basophils. The preincubation of basophils with neurokinin-1 (NK-1) or -2 (NK-2) receptor antagonists revealed the SP effect to act via NK-1 receptors in basophils. In addition, we were able to show phosphodiesterases and phosphoinositide-3 kinases to be engaged in the downstream signalling pathway. Our observations reveal for the first time a link between basophils, which are engaged in allergic processes, and the neuropeptides SN and SP. Furthermore, our data might suggest phosphodiesterases or phosphoinositide-3 kinases to be new therapeutic targets for the treatment of allergic diseases such as asthma or allergic rhinitis.
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PMID:Sensory neuropeptides are potent chemoattractants for human basophils in vitro. 2003 5

Hemokinin 1 (HK-1) is a substance P-like tachykinin peptide predominantly expressed in non-neuronal tissues. In addition to a prominent function in lymphoid development, recent studies indicate a potential role for HK-1 in immunoregulation. The current study was focused on its action on mature B cells. Despite the negligible effect on its own, HK-1 exhibited a profound influence on B cell activation elicited by several classical signals, including LPS stimulation, BCR cross-linking, and CD40 ligation. Cells therefore showed enhanced proliferation, survival, and CD80/86 expression, and produced more IgM with a higher frequency of Ab-forming cells. Biochemical analysis revealed that HK-1 alone was sufficient to induce the activation of MAPKs and the expression of Blimp-1 and Xbp-1 in B cells. Nevertheless, costimulation with a known B cell activator resulted in much enhanced phosphorylation of MAPKs and transcriptional activation of Blimp-1 and Xbp-1. Overall, these data support that HK-1 provides an important costimulatory signal for B cell activation, possibly through synergistic activation of the MAPK pathway and induction of transcription factors critical for plasmacytic differentiation.
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PMID:Hemokinin-1 activates the MAPK pathway and enhances B cell proliferation and antibody production. 2020 12

The transient receptor potential vanilloid 1 (TRPV1) is primarily localized to sensory nerve fibers and is associated with the stimulation of pain and inflammation. TRPV1 knockout (TRPV1KO) mice show enhanced LPS-induced sepsis compared with wild type (WT). This implies that TRPV1 may have a key modulatory role in increasing the beneficial and reducing the harmful components in sepsis. We investigated immune and inflammatory mechanisms in a cecal ligation and puncture (CLP) model of sepsis over 24 h. CLP TRPV1KO mice exhibited significant hypothermia, hypotension, and organ dysfunction compared with CLP WT mice. Analysis of the inflammatory responses at the site of initial infection (peritoneal cavity) revealed that CLP TRPV1KO mice exhibited: 1) decreased mononuclear cell integrity associated with apoptosis, 2) decreased macrophage tachykinin NK(1)-dependent phagocytosis, 3) substantially decreased levels of nitrite (indicative of NO) and reactive oxygen species, 4) increased cytokine levels, and 5) decreased bacteria clearance when compared with CLP WT mice. Therefore, TRPV1 deletion is associated with impaired macrophage-associated defense mechanisms. Thus, TRPV1 acts to protect against the damaging impact of sepsis and may influence the transition from local to a systemic inflammatory state.
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PMID:TRPV1 deletion enhances local inflammation and accelerates the onset of systemic inflammatory response syndrome. 2254


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