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)

We examined the effect of respiratory tract infection with Sendai virus on the responsiveness of airway blood flow to substance P (SP) in rats. Pathogen-free rats were inoculated with either Sendai virus suspension or sterile viral growth medium into each nostril. Five days later, we measured airway and esophageal blood flows before and immediately after injection of SP or histamine into the left ventricle of rats in both groups using a modification of the reference-sample microsphere technique. Viral infection potentiated the increase in airway blood flow evoked by SP but not by histamine. We also examined the effect of neutral endopeptidase (NEP) and angiotensin-converting enzyme (ACE) on the SP-induced increase in airway blood flow. Both phosphoramidon (NEP inhibitor) and captopril (ACE inhibitor) potentiated the increase in airway blood flow produced by SP in pathogen-free rats. In the presence of both peptidase inhibitors, a submaximal dose of SP increased blood flow to a similar level in infected and pathogen-free rats. Thus decreased activity of both ACE and NEP may be involved in the exaggerated increase in airway blood flow evoked by SP in virus-infected rats.
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PMID:Viral infection potentiates the increase in airway blood flow produced by substance P. 759 94

Upper respiratory tract virus infections may enhance airway responsiveness to histamine in normal subjects. We have studied the effects of parainfluenza Type I (Sendai) virus infection of the upper respiratory tract on the airway responsiveness to acetylcholine (ACh) and substance P administered by either the inhaled or intravenous route in the anesthetized guinea pig. Airway responses to electrical stimulation of the vagus nerves in the presence of atropine (1 mg.kg-1 i.v.) were also studied. After four to five days following virus infection, mean pulmonary insufflation pressure increased significantly in response to inhaled ACh compared to that in control animals. Responses to intravenous ACh were not enhanced. By contrast, responses to both intravenous and inhaled substance P were increased. In addition, mean pulmonary insufflation pressure after electrical stimulation of the vagus nerves for 30 seconds at 5 V, 5 msec (frequencies of 3, 10, and 30 Hz) were all enhanced after virus infection. We conclude that the increased airway responsiveness observed to the exogenous administration of the neurotransmitters ACh and substance P after viral respiratory infection may be due to different mechanisms possibly associated with an interference with the epithelium.
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PMID:Airway hyperresponsiveness to acetylcholine and to tachykinins after respiratory virus infection in the guinea pig. 768 Aug 45

Although sensory nerve activity may be important to the human airway in numerous possible ways, the relevance of "neurogenic inflammation" to the onset and development of asthma is unknown. However, several of the symptoms of asthma (bronchoconstriction, cough, and dyspnea) have a neuronal component that can be modeled in the laboratory by various stimuli that are thought to invoke sensory nerve activation. Nedocromil sodium is highly effective against bronchoconstriction induced by bradykinin, the tachykinins substance P and neurokinin A, and sulfur dioxide and metabisulfite. The results for induced cough in healthy subjects are equivocal, although the drug is effective on spontaneously occurring cough in patients with asthma. Nedocromil sodium had a modest but significant effect on symptoms associated with episodes of viral infection.
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PMID:Clinical effects of nedocromil sodium on challenges invoking neuronal mechanisms and on virally induced symptoms. 893 89

Advances in the understanding of neural mechanisms in asthma may provide novel therapeutic approaches in the treatment of asthma. Excessive activity of cholinergic nerves may be important in asthma. Dysfunction of M2 muscarinic receptors in asthma may lead to excessive bronchoconstriction and mucus secretion and can be induced in animal models by a range of stimuli including allergen, viral infection, ozone, eosinophil products and cytokines. Cholinergic mechanisms may be especially important in certain types of patients and anticholinergic agents provide protection against bronchospasm due to psychogenic factors or beta2-blockers. Non-adrenergic non-cholinergic (NANC) mechanisms, both inhibitory (i-NANC) and excitatory (e-NANC), may play a significant role in the pathophysiology of asthma. The putative neurotransmitters, vasoactive interstinal polypeptide (VIP) and nitric oxide (NO), mediate neural bronchodilation in human airways. There does not appear to be a defect in the i-NANC system in moderate or severe asthma. e-NANC is mediated by the sensory neuropeptides substance P (SP) and the more potent bronchoconstrictor neurokinin A (NKA). Various studies suggest that the SP content of human airways is increased in asthma. Tachykinins are not only present in sensory nerves, but also are produced by inflammatory cells such as alveolar macrophages, dendritic cells, eosinophils, lymphocytes and neutrophils. They can be released into the airways by stimuli such as allergen and ozone. Evidence suggests that in addition to smooth muscle contraction, which is mediated mainly by NK2 receptors, tachykinins also cause mucus secretion, plasma extravasation and stimulate inflammatory and immune cells. These effects are mediated by NK1 receptors. Recent studies have shown that NK2 receptor antagonists such as saredutant partially inhibit NKA-induced bronchoconstriction in asthmatics. Thus, tachykinin receptor antagonists have potential as therapies for asthma.
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PMID:Neural mechanisms in asthma. 1084 78

Tachykinins function not only as neurotransmitters but also as immunological mediators. We used infection of tachykinin-deficient (PPT-A(-/-)) mice and wild-type controls with murine gammaherpesvirus to assess the role of tachykinins in the host response to a virus infection. Although infection was ultimately controlled in PPT-A(-/-) mice, there were higher titers of infectious virus in the lungs, accompanied by a more rapid influx of inflammatory cells. Clearance of latently infected cells from the spleen was also delayed. This is the first report of the direct influence of tachykinins in the host response to a virus infection.
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PMID:Role of tachykinins in the host response to murine gammaherpesvirus infection. 1158 15

The present study assessed the functional consequences of viral infection with a neurotropic coronavirus, designated MHV OBLV, that specifically targets central olfactory structures. Using standard operant techniques and a 'go, no-go' successive discrimination paradigm, six BALB/c mice were trained to discriminate between the presentation of an air or odor stimulus (three mice for each of the odorants propanol and propyl acetate). Two additional BALB/c mice were trained to discriminate between the presentation of air and the presentation of either vanillin or propionic acid. Following criterion performance, each mouse received an additional 2000 trials of overtraining. At completion of overtraining one mouse from the propanol and propyl acetate groups were allocated as untreated. The remaining six mice were inoculated with 300 microl of the OBLV stock per nostril for a total of 1.5 x 10(6) p.f.u. in 600 microl. Following a 1 month rest, untreated and inoculated animals were again tested on their respective air versus odor discrimination task. Untreated animals immediately performed at criterion levels. In contrast, inoculated animals varied in their capacity to discriminate between air and odorant. Five of the six inoculated mice showed massive disruption of the olfactory bulb, including death of mitral cells; the other was more modestly affected. In addition, the density of innervation of the olfactory mucosa by substance P-containing trigeminal fibers is also affected by inoculation. Those mice that remained anosmic to the training odorants had the most severe reduction in mitral cell number and substance P fiber density among the inoculated animals.
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PMID:Functional consequences following infection of the olfactory system by intranasal infusion of the olfactory bulb line variant (OBLV) of mouse hepatitis strain JHM. 1159 72

Immunohistochemistry was combined with retrograde labeling to characterize the effect of respiratory infection with Sendai virus on the number of Substance P/Neurokinin A-containing vagal afferent neurons whose cell bodies resided in the nodose ganglia and whose receptive fields were located in guinea pig trachea. Of the neurons labeled from the trachea of vehicle-inoculated guinea pigs, few stained positively for Substance P/Neurokinin A (approximately 3% of total labeled neurons). These neurons had small diameter cell bodies (mode = 16-20 microm), a feature of nociceptive-like C-fibers. Viral infection (Day 4 after inoculation) was associated with a significantly greater number of labeled neurons containing Substance P/Neurokinin A (approximately 20% of total labeled neurons). The majority of these had a relatively large cell body diameter (mode = 36- 40 microm), a feature of nonnociceptive afferent neurons. This induction appeared to be reversible as there were significantly fewer Substance P/Neurokinin A positive neurons in nodose ganglia from virus-inoculated guinea pigs at Day 28 after inoculation, a time point when virus-induced airway inflammation had all but resolved. These findings support the hypothesis that viral infection leads to a qualitative change in the vagal afferent innervation of guinea pig airways such that both small diameter nociceptive-like neurons and large diameter nonnociceptive neurons express tachykinins.
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PMID:Expression of tachykinins in nonnociceptive vagal afferent neurons during respiratory viral infection in guinea pigs. 1195 47

Substance P (SP), a potent modulator of neuroimmunoregulation, exerts its activity by binding to the neurokinin-1 receptor (NK-1R). The SP-NK-1R interaction is important in inflammation and viral infections, including HIV infection of human immune cells. We recently demonstrated that SP modulates HIV replication and that a non-peptide SP antagonist CP-96,345 inhibits HIV replication in human monocyte-derived macrophages (MDM) by affecting the SP-NK-1R interaction. In order to examine the effect of the SP antagonist on SP mRNA expression, MDM was incubated with or without CP-96,345 in the presence or absence of HIV infection. SP mRNA expression in these cells was then determined by real-time PCR technology. The effect of CP-96,345 on chemokine gene expression was also investigated by using a cDNA array assay. CP-96,345 down-regulated SP mRNA expression and antagonized exogenous SP-enhanced SP expression at the mRNA level, suggesting that SP autocrine regulation was interrupted by CP-96,345. CP-96,345 inhibited HIV replication in MDM, associated with down-regulated SP mRNA expression in comparison to HIV infection controls. In parallel with down-regulated SP and CCR5 mRNA expression, cDNA array assays indicated that CP-96,345 treatment also inhibited IL-8 gene expression, while enhancing expression of fractalkine and monocyte chemotactic protein-3 (MCP-3). Since SP plays an important role in inflammation and viral infections, these studies may have potential applications for therapeutic intervention of inflammation and viral infection of immune cells.
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PMID:A non-peptide substance P antagonist down-regulates SP mRNA expression in human mononuclear phagocytes. 1209 17

One component of the protective host response against mucosal pathogens includes the local production and increased expression of certain neuropeptides and their receptors. The present study further demonstrates this fact by investigating the contribution that substance P receptor expression makes toward immunity against a gamma-herpesvirus infection. Following intragastric inoculation with murine gamma-herpesvirus 68 (gamma HV-68), expression of substance P and its receptor was increased in mucosal and peripheral lymphoid organs in wild-type strains of mice. These results suggested that this receptor/ligand pair might be an important component of the host response against this viral infection. Such a hypothesis was supported by the demonstration that mice, genetically deficient in substance P receptor expression, showed an increased viral burden when compared with syngeneic C57BL/6 mice. Furthermore, substance P receptor-deficient mice showed a reduced CTL response against gamma HV-68, suggesting a mechanism to explain this increased viral burden. Such limitations in the Ag-specific CTL response in substance P receptor-deficient mice could result from lowered expression of IL-12 during viral infection. Consistent with this hypothesis, increases in mRNA encoding IL-12 and secretion of this cytokine into sera of infected, wild-type animals were markedly reduced in substance P receptor-deficient mice. These studies demonstrate that genetic elimination of substance P receptors in mice results in an increased gamma-herpesvirus burden and an altered host response.
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PMID:Reduced CTL response and increased viral burden in substance P receptor-deficient mice infected with murine gamma-herpesvirus 68. 1259 88

Following viral infection, the expression of substance P and its receptor can contribute significantly to the resulting host response. For gammaherpesvirus infection of mice, the presence of this tachykinin and its receptor contributes to the protective host response. It is likely that this augmentation of the immune response is directed toward the developing T helper type 1 response and cytotoxic T lymphocyte activation. However it has also been shown that the presence of substance P and its receptor may contribute to viral diseases by facilitating viral replication or by contributing to a destructive inflammatory response. Specifically, the presence of substance P can augment replication of HIV in cultured macrophages, which is especially significant since levels of this tachykinin are elevated in patients with this viral disease. Furthermore, rodent models of paramyxovirus infection have demonstrated that the presence of neurokinin receptors and their ligands contributes to the destructive inflammatory response in airways. Taken together, these studies demonstrate a surprising role for substance P and the neurokinin-1 receptor in the host response following these viral infections.
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PMID:Tachykinin-modulated anti-viral responses. 1535 65


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