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)

The IV injection of neurotensin (NT) into anesthetized rats produced a marked increase in hematocrit, labored breathing and peripheral blood stasis with cyanosis. This effect could also be produced by the NT-related peptides, neuromedin-N and xenopsin; however, it was not observed when nine other biologically active peptides, including bradykinin and substance P, were tested. Associated with these responses were increases in the plasma levels of histamine (measured radioenzymatically) and the leukotrienes, LTB4, LTC4, LTD4, and LTE4 (measured by RIA and HPLC). The increment in hematocrit after varying doses of NT correlated to the increase in plasma levels of LTC4. Histamine and LTC4 were both capable of elevating hematocrit when given IV; however, LTC4 was approximately 1000 times more potent than histamine and active doses of histamine elevated LTC4 levels. Furthermore, the effects of NT on plasma LTC4 and hematocrit were reduced by pretreating animals with antagonists to histamine and serotonin. Pretreatment with the specific mast cell degranulating agent, compound 48/80, also blocked NT's ability to elevate plasma levels of histamine, LTB4 and LTC4 and prevented the increased hematocrit and cyanosis. These results indicate that NT-related peptides are very potent and specific stimulators of leukotriene release and that this action is mediated by mast cells and associated with loss of plasma volume and blood stasis. A working hypothesis is that histamine, released from mast cells in response to NT, stimulates LTC4 production by other cells.
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PMID:Neurotensin elevates hematocrit and plasma levels of the leukotrienes, LTB4, LTC4, LTD4 and LTE4, in anesthetized rats. 166 83

We examined the effect of dexamethasone on A23187-induced bronchospasm, pulmonary inflammation and airway responses to substance P. Guinea pigs, dosed orally once a day for 4 days with dexamethasone (3.0, 10.0 or 30.0 mg/kg) or saline, were exposed to an aerosol of A23187 for 12 min or until labored breathing began. Postmortem pulmonary gas trapping was used as an indicator of in vivo airway obstruction and changes in bronchial responses. Dexamethasone did not alter airway obstruction or inflammation 1 h after A23187 exposure. However, dexamethasone reduced the enhanced airway responses to substance P and bronchiolar/peribronchiolar inflammation 24 h post-A23187. It is possible that glucocorticosteroid suppression of A23187-induced pulmonary inflammation was important in reducing the increased airway responses to substance P.
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PMID:Effect of dexamethasone on A23187-induced airway responses in the guinea pig. 751 51

We examined the effect of A23187-induced lung injury on airway responses to a variety of bronchoconstrictive aerosols in conscious guinea pigs. Guinea pigs were exposed to aerosolized A23187 or vehicle for 12 min or until labored breathing began. Animals were allowed to recover for 24 h, and then they were challenged with inhaled histamine, leukotriene D4 (LTD4), platelet-activating factor (PAF), or substance P. Eight minutes after start of the bronchoprovocative aerosol, the guinea pigs were killed and excised lung gas volume (ELGV) measurements were used as an index of in vivo airway obstruction. No differences in ELGV dose-response curves to LTD4 were seen in A23187- and vehicle-exposed animals. A23187 exposure produced small increases in both histamine and PAF sensitivity. However, A23187 caused a much more pronounced leftward shift in the dose-response to substance P. Coadministration of the neutral endopeptidase inhibitor, thiorphan, did not reduce the A23187-related airway responses to substance P. Histologic evaluation of A23187-treated lungs revealed peribronchiolar inflammation, bronchiolar epithelial injury, and mild alveolitis. We conclude that A23187 treatment produces differential airway responses to bronchoactive agents, with a preferential sensitization to substance P.
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PMID:Inhaled A23187 produces a preferential sensitization to substance P. 767 72

We tested the hypothesis that allergen-induced mediator release augments the magnitude of isocapnic dry gas hyperpnea-induced bronchoconstriction in sensitized guinea pigs. Male Hartley guinea pigs were sensitized by spontaneous inhalation of ovalbumin (OA) aerosol on days 0 and 7 of the study. On day 14, sensitized animals again breathed OA aerosol and were prospectively divided into a group that exhibited labored breathing (LB), presumably reflecting OA-induced inflammatory mediator release, and a group that did not exhibit LB at this time. Control guinea pigs breathed saline aerosol on days 0, 7, and 14. Bronchoalveolar lavage on day 17 disclosed relative eosinophilia in OA+LB, but not in OA-LB, animals. On day 17, the bronchoconstrictor responses to increasing intravenous (i.v.) doses of acetylcholine (ACh), substance P (SP), neurokinin A (NKA), and capsaicin, as well as dry gas hyperpnea, were measured in vivo in animals from each group. Control and OA-LB guinea pigs exhibited similar responses, but OA+LB animals demonstrated augmented bronchoconstriction induced by i.v. administration of ACh, SP, or NKA. However, despite their augmented responsiveness to these exogenous constrictor agonists, OA+LB animals displayed no greater bronchoconstriction after dry gas hyperpnea or i.v. capsaicin administration. It is known that both dry gas hyperpnea and i.v. capsaicin cause bronchoconstriction in guinea pigs by releasing endogenous tachykinins from airway sensory C-fibers. Thus, our results suggest that allergen-induced mediator release impairs endogenous tachykinin release from airway sensory C-fibers in guinea pigs.
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PMID:Impaired sensorineural function after allergen-induced mediator release. 768 1