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)

Non-adrenergic non-cholinergic (NANC) nerves are the third nervous system in the lung. There are increasing evidences that the main transmitters of NANC inhibitory (NANC-i) nerves and NANC excitatory (NANC-e) nerves are vasoactive intestinal peptide (VIP) and substance P (SP) respectively. We measured the levels of plasma VIP. SP and bronchial responsiveness in the patients with asthma. Chronic bronchitis and healthy subjects. The results showed that VIP level is decreased and negatively correlated with airway resistance, whereas SP level is increased and positively correlated with bronchial hyperresponsiveness (BHR) in asthma. It is suggested that overexcitation of NANC-e nerves and deficiency of NANC-i nerves are closely related with asthma attack and BHR.
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PMID:[A clinical study on the effect of non-adrenergic non-cholinergic nerves in asthma]. 751 57

Airway responsiveness is increased in a variety of airway diseases. To understand the mechanism of enhanced airway responsiveness, in particular as it pertains to asthma, animal models have been developed and extensively explored. The guinea pig and Basenji-greyhound dog are the best characterized animals showing airways hyperresponsiveness and appear to bear substantial resemblances to asthmatic human subjects. Challenge with bronchoconstrictive agonist results in bronchoconstriction and transient vascular leak. Both phenomena contribute to the degree of airway narrowing. Adenosine challenge tests not only the responsiveness of the airways, but also that of the airway effector cells such as the mastocyte. Bradykinin and tachykinin cause indirect airway narrowing, probably by liberation of leukotrienes. Responsiveness can be enhanced by immune and non-immune challenges. Ozone, Sephadex, various contractile agonists (leukotriene D-4, bradykinin, platelet-activating factor), as well as certain cytokines (IL-1, IL-2, TNF-alpha) can enhance airway responsiveness. Cyclooxygenase and lipooxygenase products appear to be involved. Allergen-induced hyperresponsiveness is associated with airway inflammation and appears to involve bradykinin and PAF acutely and growth of airway smooth muscle chronically.
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PMID:[Animal models of bronchial hyperreactivity]. 751 8

We studied the effect of cilostazol, a cyclic nucleotide phosphodiesterase (PDE) III inhibitor, on a substance P (SP)-induced increase in lung resistance and in airway microvascular leakage in guinea pigs in vivo. Four minutes after intravenous (i.v.) administration of cilostazol (1.5 and 5 mg/kg) or vehicle, Evans blue dye (20 mg/kg) was given i.v. One minute later, 30 nmol/kg SP was administered i.v. The SP-induced increase in lung resistance was measured for 6 min. Following the measurement of lung resistance, microvascular leakage at the trachea, main bronchi and intrapulmonary airways was also examined. Cilostazol attenuated the SP-induced increase in lung resistance, with a significant inhibition at the concentration of 5 mg/kg. Five milligrams per kilogram cilostazol also significantly inhibited SP-induced Evans blue dye extravasation at the trachea and main bronchi. These results suggest that cilostazol might reduce airflow obstruction which is seen in diseases such as asthma through attenuation of bronchoconstriction and, possibly, airway edema resulting from airway microvascular leakage in man.
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PMID:Effects of cilostazol, a cyclic nucleotide phosphodiesterase III inhibitor, on substance P-induced airflow obstruction and airway microvascular leakage in guinea pigs. 751 49

Substance P (SP) stimulates human skin and rodent mast cells. Since neuropeptide-mediated reflexes may be important in asthma, the ability of SP to stimulate human mast cells obtained at bronchoalveolar lavage (BAL) was examined. Routine BAL (n = 22) samples were obtained and histamine release experiments performed in a standard manner. Spontaneous histamine release was bimodally distributed (Group A, high spontaneous release/Group B, normal spontaneous release). Further, Group A had significantly elevated corrected SP-induced histamine release compared to Group B but the corrected calcium ionophore A23187-induced responses were similar. No differences were found in clinical history, age, lavage return or total cell numbers between groups. However, differential cell counts revealed significantly elevated mast cell numbers in Group A providing further evidence for altered mast cell responsivity associated with mast cell hyperplasia. In asthma, BAL mast cells have increased spontaneous and stimulated secretory responses; thus, in asthma SP may also stimulate pulmonary mast cells.
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PMID:Differential reactivity of human bronchoalveolar lavage mast cells to substance P. 752 45

We tested the hypothesis that the inhaled tachykinin substance P (SP) can induce hyperresponsiveness to methacholine in asthmatic subjects in vivo. Nine atopic nonsmoking asthmatic males with normal forced expiratory volume in 1 s (FEV1; > 80% predicted) and increased methacholine sensitivity [provocative concn causing 20% fall in FEV1 (PC20) < 8 mg/ml] participated in a two-period placebo-controlled crossover study. Dose-response curves to SP (0.25-8 mg/ml) and placebo were recorded on 2 randomized days at least 1 wk apart, and methacholine tests were done 24 h before and 2 and 24 h after these challenges. The responses were measured by FEV1 (%fall from baseline). The position of the methacholine dose-response curves was expressed by the PC20 FEV1 and by the maximal response by the plateau level (MFEV1). SP caused a dose-dependent fall in FEV1 (P < 0.001). There was a slight increase in the PC20 FEV1 at 2 and 24 h, which was not significantly different between placebo and SP. Similarly, there was a reduction in MFEV1 at 2 h after both pretreatments. However, at 24 h after SP inhalation, MFEV1 increased compared with placebo. These changes in MFEV1 were significantly different between SP and placebo by 5.2 +/- 2.2% fall (SE) (P < 0.05). We conclude that 1) a bronchoconstrictive dose of SP, compared with placebo, enhances maximal airway narrowing to methacholine in asthma 24 h after inhalation and 2) tolerance develops to high doses of inhaled methacholine. These findings are suggestive of a role of SP in causing excessive airway narrowing in asthma by inflammatory mechanisms.
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PMID:Effects of inhaled substance P on airway responsiveness to methacholine in asthmatic subjects in vivo. 753 Jul 6

Tracheal and lung parenchymal SP-LI (substance P-like immunoreactivity) and VIP-LI (vasoactive intestinal peptide-like immunoreactivity) content was measured in HPLC-purified tissue extracts from patients with and without asthma. We detected significantly less SP-LI in tracheal tissue from asthmatic than from nonasthmatic patients, whereas parenchymal SP-LI content was not significantly different between these groups. This finding does not support the concept that asthmatic lungs contain excessive amounts of SP. Indeed, lower SP-LI content of tracheal tissues from asthmatic patients may reflect augmented SP release followed by degradation. We detected greater quantities of VIP-LI in tracheal than in parenchymal tissue in both groups, but did not detect significant differences in VIP-LI content in tracheal or parenchymal tissues from asthmatic and nonasthmatic patients. These findings indicate that asthmatic and nonasthmatic lungs contain similar levels of VIP.
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PMID:Neuropeptide content of lungs from asthmatic and nonasthmatic patients. 753 Nov

An increase in subepithelial mesenchymal cells and associated connective tissue is a feature of bronchial asthma. We determined whether neuropeptides could modulate fibroblast activity, particularly with respect to proliferation and chemotaxis. Human lung fibroblasts were cultured with neurokinin A (NKA), substance P (SP), vasoactive intestinal peptide (VIP), and calcitonin-gene-related peptide (CGRP). After 48 h, fibroblast proliferation was measured by a colorimetric assay based on the uptake and subsequent release of methylene blue. The chemotactic response to neuropeptides was determined with the use of a modified Boyden chamber. Both NKA and SP (10(-7)-10(-4) M) stimulated human lung fibroblast proliferation in HFL1 and IMR-90 fibroblasts. VIP and CGRP had no effect on fibroblast proliferation. NKA alone stimulated fibroblast chemotaxis maximally at 10(-10) M. Neutral endopeptidase (NEP) activity of 0.52 and 5.2 pmol/10(6) cells was assayed in IMR-90 and Hs68 fibroblasts, respectively. Phosphoramidon (5 x 10(-6)-10(-5) M), an NEP inhibitor, enhanced fibroblast proliferation in a dose-dependent manner. Thus neuropeptides have the potential to cause activation of mesenchymal cells, and neuropeptide release may contribute to the structural abnormalities observed in asthmatic airways.
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PMID:Effects of neuropeptides on human lung fibroblast proliferation and chemotaxis. 753 71

In experimental studies, tachykinins, especially substance P (SP), cause many of the pathophysiological features of neurogenic inflammation. It is unclear whether these peptides are involved in human airway inflammation in diseases such as asthma and chronic bronchitis. To elucidate the relation between neurogenic inflammation and airway inflammatory diseases, we examined the SP concentration in sputum after hypertonic saline inhalation challenge in patients with asthma, patients with chronic bronchitis, and normal volunteers. SP concentration was measured by radioimmunoassay. The sputum SP concentration was significantly higher in patients with asthma (mean +/- SEM, 17.7 +/- 2.4 fmol/ml; p < 0.01) and patients with chronic bronchitis (25.6 +/- 5.5 fmol/ml; p < 0.01) than in normal volunteers (1.1 +/- 0.4 fmol/ml). In patients with asthma, the SP concentration was significantly related to the eosinophil cell count in induced sputum. In all subjects, the SP concentration in induced sputum correlated with FEV1/FVC. These data suggest that neurogenic inflammation may be involved in the airway inflammatory process and subsequent airway narrowing not only in asthma but also in chronic bronchitis.
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PMID:Elevated substance P content in induced sputum from patients with asthma and patients with chronic bronchitis. 753 1

Substance P elicits histamine release from human skin and rodent mast cells. Since neuropeptide-mediated reflexes may be important in asthma, we examined the ability of substance P to stimulate human mast cells obtained at bronchoalveolar lavage (BAL). BAL samples were obtained at routine bronchoscopy from 35 non-preselected patients. Histamine release experiments were performed in a standard manner using substance P and the calcium ionophore A23187. Both substance P (50 microM) and A23187 caused histamine release (median 26.7% range 6.2-62.8% and 32.1%, 7.7-56.8% respectively) which was significantly greater (P < 0.0001) than the spontaneous release (median 15.6%, range 4.1-33.4%), i.e. that in the absence of any stimulus. Substance P induced histamine release was via an energy dependent process and was blocked by preincubation with antimycin A. A significant correlation was observed between substance P induced release and spontaneous release but was not observed with A23187 induced release. Mast cell counts correlated significantly with substance P induced release but not with spontaneous or A23187 induced release. The substance P induced histamine secretion was elicited at similar concentrations to those used with rodent and human skin mast cells. Asthma is associated with increased numbers of mast cells which have both increased spontaneous and stimulated secretory responses. Thus, in vivo, the bronchoconstrictor action of substance P may in part result from activation of mast cells in the bronchial lumen.
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PMID:Substance P induces histamine release from human pulmonary mast cells. 753 43

The influence of melatonin on tension of isolated bovine pulmonary vascular and bronchial smooth muscle rings were examined in these experiments. Melatonin caused a dose-dependent relaxation of precontracted (30 mM KCl) pulmonary artery and vein, although the effect is greater in arterial smooth muscle. This relaxant response was blocked by preincubating vessels with antagonists of vasoactive intestinal peptide or Substance P. In bronchial smooth muscle, melatonin caused a small contractile response. These experiments demonstrate that in response to melatonin the pulmonary vasculature relaxes, while in airway smooth muscle the reverse, constriction, occurs. It is hypothesized that nocturnal exaggeration of asthma may, in part, be due to changes in circulating levels of melatonin.
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PMID:Influence of melatonin on bovine pulmonary vascular and bronchial airway smooth muscle tone. 754 81


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