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 ability of substance P, neurokinin A and its C-terminal fragment, neurokinin A-(4-10), to elicit NK-1 (salivation) and NK-2 (bronchospasm) receptor-mediated responses was investigated in anaesthetized guinea-pigs. Neurokinin A-(4-10) produced a dose-related increase in tracheal insufflation pressure and its maximal effect was similar to that elicited by neurokinin A and significantly greater than that of substance P. On the other hand substance P induced a potent dose-dependent increase of salivation while neurokinin A was significantly less potent. Neurokinin A-(4-10) did not exert any sialologic effect even at the dose of 100 nM/kg. These findings indicate that neurokinin A-(4-10) might be a valuable pharmacological tool for characterizing the involvement of NK-1 and NK-2 receptors in physiological responses in vivo.
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PMID:Neurokinin A-(4-10): a potent bronchospastic agent virtually devoid of sialologic properties in anaesthetized guinea-pigs. 245 32

Several studies have demonstrated that neuropeptides are present in peptidergic fibres of bronchial tissue. The aim of the present study was to evaluate in vivo the effect of nedocromil sodium (2 x 2 mg) on bronchospasm induced by inhalation of substance P. Six moderate asthmatic patients, mean age 25.17 years, were studied. Airway response was measured as FEV1 and the dose of substance P (using a dose range of 23-736 nmol) producing a 20% decrease in FEV1 (PD20) was calculated from the individual semilogarithmic dose-response curves. Patients were studied on 3 separate days in a randomized, double-blind manner. On the first day a baseline PD20 value was determined. On subsequent days substance P challenge was performed after pretreatment (20 min before challenge) with either placebo or nedocromil sodium. Student's paired t-test and Wilcoxon's test were used for statistical analysis. The results of this study demonstrated that inhalation of substance P causes a dose-dependent bronchoconstriction and that the bronchoconstriction induced by substance P can be prevented by pre-treatment with nedocromil sodium.
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PMID:Effect of nedocromil on bronchospasm induced by inhalation of substance P in asthmatic subjects. 245 98

The aim of this study was to evaluate in vivo the effect of inhaled substance P (SP) and to determine the effect of sodium cromoglycate (SCG) on bronchospasm induced by its inhalation in 6 asthmatic patients. At the beginning of the study, all patients were asymptomatic, with an FEV1 value not less than 20%. SP was administered as aerosol, prepared in 0.9% saline to produce a dose range of 0.03-1 mg. Airway response was measured as FEV1 using a pulmonary system 47120A Hewlett-Packard instrument. The dose of SP producing a 20% change in FEV1 was calculated from the individual semi-logarithmic dose-response curve (PD20). After administration of the placebo, SP produced a dose-related bronchoconstriction with a geometric mean PD20 of 0.15 mg. After SCG, the mean PD20 value was of 0.64 mg (p less than 0.01). These results confirmed the bronchospasm induced by inhalation of SP and demonstrated that SCG is able to prevent this effect although it is impossible to define the exact mechanism of the drug.
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PMID:Bronchospasm induced by inhalation of substance P: effect of sodium cromoglycate. 246 15

The interaction of threshold doses of bradykinin (BK) and substance P (SP) with acetylcholine (ACh)-induced bronchospasm was investigated in anaesthetized guinea-pigs. The two peptides potentiated the ACh-induced bronchospasm, an effect which did not seem to depend on prostaglandin release. On the other hand, vagotomy abolished the capacity of BK and SP to potentiate the ACh-induced bronchospasm. The present data suggest a possible involvement of BK and SP in the genesis of airway hyperreactivity.
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PMID:Bradykinin and substance P potentiate acetylcholine-induced bronchospasm in guinea-pig. 247 66

Pulmonary hyperreactivity is a common feature in asthma. In the present study we investigated the possible role of different mediators in the genesis of this phenomenon. In particular the ability of prostaglandin D2 (PGD2), substance P (SP) and bradykinin (BK) to potentiate acetylcholine (ACh)-induced bronchospasm was assessed in anaesthetized and mechanically ventilated guinea-pigs. Threshold doses of PGD2, SP and BK significantly enhanced ACh-induced bronchospasm in normal guinea-pigs, even if a different trend in the onset and duration of the phenomenon was observed. Ovalbumin (OA) active sensitization modified the ability of the three compounds tested to positively interact with ACh. Beta-adrenoceptor blockade due to propranolol treatment increased the positive interaction between the three compounds and ACh. The role of PGD2, SP and BK in the genesis of pulmonary hyperreactivity is proposed and the relevance of mediator-mediator interaction during adrenergic imbalance is discussed.
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PMID:Role of the mediators in pulmonary hyperreactivity: the cocktail interaction hypothesis. 247 37

Many agents are capable of mast cell activation (MCA). In the lung, exposure to allergens induces IgE-mediated mast cell degranulation. By this process, chemical mediators are released and attract inflammatory cells that infiltrate the airway wall. This immune response is a potent stimulus for the pathologic changes seen in asthma (e.g., bronchospasm, mucosal edema, airway hyperreactivity, and mucus secretion). One neglected component of the asthmatic response is vascular permeability--the hallmark of mast cell degranulation. Like muscle contraction, vascular permeability occurs rapidly in response to an antigen challenge and is prevented by classic antiasthmatic therapy. Studies with antidromic nerve stimulation have indicated a relationship between MCA and the histamine-induced release of the sensory neuropeptide substance P, which causes vasodilation. Mediators released during the immediate hypersensitivity reaction may attract neutrophils and other chemotactic factors involved in the late allergic response, which includes a recrudescence of MCA caused by the release of histamine-releasing factors. Understanding these pathophysiologic events in asthma will be useful in formulating therapy.
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PMID:Asthma and mast cell activation. 264 47

Sympathetic and parasympathetic influences on the airway resistance under physiological and pathophysiological conditions have long been known. In recent years, this classical view had to be extended due to mounting evidence of neurocrine and paracrine peptide mediators. The term non-adrenergic non-cholinergic (NANC) nervous system was coined. Besides other effects the non-adrenergic mediators (e.g. VIP and PHI/PHM) give rise to bronchodilation, while the non-cholinergic modulators (SP, neurokinin A, and CGRP) induce bronchospasm. The axon-reflex theory postulates liberation of non-cholinergic peptide substances by afferent C-fibers exposed by bronchial epithelial cell damage as one important cause of bronchial obstruction. In addition to biogenic amines, such peptides as bombesin, leu-encephalin, beta-endorphin, calcitonin, doctrine cells of the bronchial epithelium. Our knowledge of the biological relevance of these mediators is at present very sketchy. Platelet activating factor (PAF) is released by alveolar macrophages, granulocytes, blood vessel endothelium, and platelets. The inhalation of PAF induces bronchospasm in healthy subjects and asthmatics and also prolonged bronchial hyperreactivity. The many factors influencing bronchial reactivity need to be classified by further investigations of the mode of interaction and interdependence of known and new mediators.
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PMID:[The significance of endocrine, neurocrine and paracrine mediators in the regulation of bronchial reactivity]. 268 1

Capsaicin, the active principle of hot peppers of the genus Capsicum, exhibits broad bioactivity. It targets neuronal structures which contain substance P, clinically seen as gastrointestinal and dermatologic irritation, bronchospasm and fibrinolysis. As a research tool, capsaicin profoundly alters neurologic anatomy and function. We review the toxicity of capsaicin and comment briefly on the use of hot peppers in child abuse.
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PMID:Capsicum and capsaicin--a review: case report of the use of hot peppers in child abuse. 332 91

To examine endogenous factors affecting the development of the massive bronchoconstriction in the postmortem guinea pig lung, 58 anesthetized open-chest animals were divided into three groups: 1) exsanguination only (n = 13), 2) pulmonary perfusion with 5% dextran and 1% bovine serum albumin (BSA) in Tyrode's solution (Ca2+ perfusate) (n = 21), and 3) pulmonary perfusion with 5% dextran and 1% BSA in saline (Ca2+-free perfusate) (n = 24). These groups were further divided into several subgroups according to treatments: 1) substance P depletion by chronic administration of capsaicin, 2) acute capsaicin treatment to release substance P, 3) dazoxiben treatment to block endogenous synthesis of thromboxane A2, 4) diethylcarbamazine treatment to eliminate leukotriene (LT) synthesis, and 5) FPL 55712 treatment to antagonize actions of LT. Vital capacity from the deflation pressure-volume (PV) curve of the lung was used as the indicator of bronchoconstriction. Most PV curves were performed for 30 min following exsanguination or artificial perfusion. Ca2+-free perfusate enhanced the airway spasm at 5-10 min, but the spasm disappeared gradually after 10 min. Substance P depletion significantly decreased (P less than 0.01) the bronchial constriction at 20-30 min, whereas substance P release induced severe airway spasm (P less than 0.01) during the entire study. In addition, FPL 55712 reduced the bronchospasm (P less than 0.05) in Ca2+ perfusate at 30 min. Thus Ca2+ and several endogenous mediators may be involved with the airway spasm of the postmortem guinea pig lung.
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PMID:Factors affecting massive postmortem bronchoconstriction in guinea pig lungs. 620 78

Extreme sensitivity of airways to multiple stimuli characterizes asthma. Airway hyperresponsiveness can be produced experimentally in otherwise healthy subjects or animals by inflammatory damage (e.g., induced by respiratory viruses or by inhaled oxidants). Evidence is presented that cell-to-cell interactions play an important role in experimental hyperreactivity and that similar inflammatory cascades may play a similar role in clinical asthma. Although the importance of epithelial cells and neutrophils has been identified in the present studies, other inflammatory mechanisms (e.g., sensory nerve release of substance P, epithelial mast cells, eosinophils) may also play key roles. In exercise-induced bronchospasm, the stimulus (e.g., cooling or drying) must affect a cell (e.g., one near the epithelial surface) by decreasing temperature or by increasing osmolality. This signal may cause mediator release and a subsequent cascade, leading to contraction of smooth muscle. Environmental irritants (e.g., ozone) inhaled during exercise may potentiate these effects by producing further inflammation.
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PMID:Inflammation and asthma. 632 24


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