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)

Airways mucociliary clearance (MCC), which continuously removes inhaled particles and cellular debris from the lungs is impaired in a number of diseases such as bronchitis, asthma and cystic fibrosis. Regulation of MCC under normal conditions is not well understood and the cause of its impairment is ill defined. Animal models have been used to study the regulatory mechanisms of both mucus secretion and MCC and to ascertain the involvement of neural pathways. Cholinergic stimulation is a most effective means of enhancing MCC in molluscs, frogs and mammals including man. Recent data from mammals suggest that MCC is also regulated by neuropeptides either directly (substance P) or by facilitating the stimulatory effect of cholinergic agents. A better understand of basic regulatory mechanisms of MCC is vital to an understanding of its impairment in respiratory diseases.
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PMID:Measurement and pharmacology of mucociliary clearance. 179 77

Neutral endopeptidase exists on the membranes of many cells in the airways. By cleaving and thus inactivating tachykinins released from sensory nerves, NEP limits the actions of these peptides. The selectivity of the enzyme is due, at least in part, to its close association with tachykinin receptors. By cleaving and inactivating the tachykinins, it limits the concentration of tachykinin that reaches the receptor. Decreased NEP activity produced by selective enzyme inhibitors, air pollutants, infections, and oxidants leads to exaggerated neurogenic inflammation. We speculate that the multiple stimuli that enter the airways of healthy individuals normally produce small, nonsymptomatic neurogenic inflammatory responses. However, when NEP activity is decreased, the responses become exaggerated and may contribute to the pathogenesis of diseases such as asthma and bronchitis.
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PMID:Decreased neutral endopeptidases: possible role in inflammatory diseases of airways. 216 84

Neuropeptides such as substance P are implicated in inflammation mediated by sensory nerves (neurogenic inflammation), but the roles in disease of these peptides and the peptidases that degrade them are not understood. It is well established that inflammation is a prominent feature of several airway diseases, including viral infections, asthma, bronchitis, and cystic fibrosis. These diseases are characterized by cough, airway edema, and abnormal secretory and bronchoconstrictor responses, all of which can be elicited by substance P. The effects of substance P and other peptides that may be involved in inflammation are decreased by endogenous neutral endopeptidase (NEP; also called enkephalinase, EC 3.4.24.11), which is a peptidase that degrades substance P and other peptides. In the present study, we report that rats with histories of infections caused by common respiratory tract pathogens (parainfluenza virus type 1, rat corona-virus, and Mycoplasma pulmonis) not only have greater susceptibility to neurogenic inflammatory responses than do pathogen-free rats but also have a lower activity of NEP in the trachea. This reduction in NEP activity may cause the increased susceptibility to neurogenic inflammation by allowing higher concentrations of substance P to reach tachykinin receptors in the trachea. Thus decreased NEP activity may exacerbate some of the pathological responses in animals with respiratory tract infections.
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PMID:Neutral endopeptidase and neurogenic inflammation in rats with respiratory infections. 254 62

Recent studies have suggested that inflammation may play an important role in the characteristic bronchial hyperresponsiveness and symptoms of chronic asthma. The mechanisms by which inflammatory cells, mediators, and nerves interact to produce the features of asthma are still uncertain, however. Although mast cells play an important role in the immediate response to allergen (and probably exercise), pharmacologic evidence argues against a critical role in the late response or bronchial hyperresponsiveness in which other cells, such as macrophages and eosinophils, may play a more important role. Many mediators have been implicated in asthma, but only PAF causes a prolonged increase in bronchial responsiveness. PAF attracts eosinophils into tissues and potently activates these cells, which may lead to epithelial damage, a key feature of asthmatic airways. PAF is also a potent inducer of microvascular leakage in airways, which may result in submucosal edema and plasma exudation into the airway lumen in the future. PAF antagonists will reveal whether PAF plays an important role in the eosinophilic inflammation of asthma. Neural mechanisms may also make an important contribution. Inflammatory mediators may influence neurotransmitter release from airway nerves, and neurotransmitters may be proinflammatory. Neural control is complex and cholinergic, adrenergic, and NANC mechanisms may contribute to bronchial hyperresponsiveness. Many neuropeptides, which may be the transmitters of NANC nerves, have been identified in airways. Neuropeptides in airway sensory nerves, such as substance P, have potent proinflammatory effects and, if these are released by an axon reflex, may amplify the inflammatory response in asthma. Since asthma may be chronic eosinophilic bronchitis, it is logical that the primary treatment should involve drugs that suppress this inflammatory response. At present, corticosteroids appear to be the most effective therapy; they have potent effects against eosinophils and macrophages (but not on mast cells) and reduce bronchial hyperresponsiveness and symptoms. By contrast, bronchodilators, such as beta-agonists, although they reduce symptoms, do not reduce the chronic inflammatory response or bronchial hyperresponsiveness and may mask the underlying inflammation. New therapies should be directed toward controlling eosinophil infiltration and activation in airways.
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PMID:New concepts in the pathogenesis of bronchial hyperresponsiveness and asthma. 265 43

We investigated whether acute exposure to nitrogen dioxide (NO2) causes major inflammatory responses (inflammatory cell recruitment, oedema and smooth muscle hyperresponsiveness) in guinea pig airways. Anaesthetised guinea pigs were exposed to 18 ppm NO2 or air for 4 h through a tracheal cannula. Bronchoalveolar lavage was performed and airway microvascular permeability and in vitro bronchial smooth muscle responsiveness were measured. Exposure to NO2 induced a significant increase in eosinophils and neutrophils in bronchoalveolar lavage fluid, microvascular leakage in the trachea and main bronchi (but not in peripheral airways), and a significant in vitro hyperresponsiveness to acetylcholine, electrical field stimulation, and neurokinin A, but not to histamine. Thus, this study shows that in vivo exposure to high concentrations of NO2 induces major inflammatory responses in guinea pig airways that mimic acute bronchitis induced by exposure to irritant gases in man.
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PMID:Bronchopulmonary inflammation and airway smooth muscle hyperresponsiveness induced by nitrogen dioxide in guinea pigs. 1042 65

Airway disorders, such as asthma and chronic obstructive bronchitis, are, in part, due to abnormalities in the nervous control of the airways. However, the ultrastructural circuitry and neurochemical anatomy of afferents modulating the output of airway-related vagal preganglionic neurons (VPNs) in the nucleus ambiguus are poorly understood. We have examined the potential role of substance P (SP) immunoreactive afferents in the regulation of anatomically identified airway VPNs. Cholera toxin b-subunit conjugated to horseradish peroxidase was used as a retrograde cell body tracer to identify the central VPNs innervating the extra-thoracic trachea. Immunocytochemistry was employed to identify SP afferents. The external formation of the nucleus ambiguus was examined by electron microscopy using a simultaneous double labeling method. Cell bodies of tracheal VPNs were 31.7 +/- 1.18 x 23.0 +/- 1.3 microm (means +/- S.E.M.) in size, contained abundant endoplasmic reticulum, had a round nucleus with a prominent nucleolus, no satellite body and displayed somatic and dendritic spines. Somato-somatic appositions, somato-dendritic appositions without intervening glial processes and dendritic "bundling" commonly seen in esophageal motoneurons were not observed. The ultrastructural morphology of tracheal VPNs were also clearly distinguishable from pharyngeal and laryngeal motoneurons in other divisions of the nucleus ambiguus which lack somatic spines. These data are consistent with the hypothesis that differences in the ultrastructure and synaptology of the different divisions of the nucleus ambiguus may be associated with specific physiological functions. The mean size (+/- S.E.M.) of SP nerve terminals was 1.57 +/- 0.06 x 0.79 +/- 0.03 microm. SP terminals formed 17.5% of the axo-dendritic and 15.9% of the axo-somatic synapses which were observed upon retrogradely labeled tracheal VPNs. Synaptic contacts observed were both symmetric and asymmetric. These synaptic interactions define, in part, the neurochemical anatomy of neuronal circuits modulating vagal preganglionic control of tracheal functions.
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PMID:Substance P afferent terminals innervate vagal preganglionic neurons projecting to the trachea of the ferret. 1195 75

Neurogenic inflammation results from activation of sensory nerves which, acting in an 'efferent' manner, release sensory neuropeptides to induce a wide variety of physiological and immunological responses. This process is easy to demonstrate experimentally in the airways of small laboratory animal species but in human airways is equivocal and, at best, minor compared with cholinergic neural control. Nevertheless, sensory neuropeptides (calcitonin gene-related peptide and the tachykinins, substance P and neurokinin A) induce airway responses in both laboratory animals and humans which suggest a potential for sensory-efferent control of human airways. In addition, there is indirect evidence for an increased 'expression' of sensory nerves and tachykinin receptors in asthma and bronchitis, which indicates that neurogenic inflammation contributes to pathophysiology of these airway conditions. In contrast, clinical trials using different classes of drugs to inhibit sensory nerve responses have failed to resolve whether neurogenic inflammation is involved in asthma, although there are concerns about the relevance of some of these studies. In contrast to their involvement in airway neurogenic inflammation, sensory nerves may be important in initiating protective reflexes, including coughing and sneezing, acting via their afferent pathways. Thus, although flickering, the concept of neurogenic inflammation in lung disease is not yet burnt out. However, it needs the rekindling of interest which re-evaluation as a protective process may bring, together with data from more appropriate clinical studies in asthma and chronic bronchitis.
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PMID:Neurogenic inflammation in lung disease: burnt out? 1765 11

The recurrent bronchitis (RB) course is caused by the bronchi secretory-evacuation mechanisms state, which provide clearance from pathogens. This mechanism can be disrupted by vegetative reflexes and neuropeptides imbalance that develops in children with the syndrome of the vertebrobasilar arterial system (SVBAS). The objective: study of the neurogenic maintenance of the RB pathogenesis in children with SVBAS by studying the serum content of substances affecting of the bronchial mucosa secretory-evacuation function and inflammatory activity (substance P, vasoactive intestinal peptide - VIP and endothelin-1 - ET-1). 90 children aged 7 to 11 years were examined, 3 observation groups were formed: Group 1 - children with RB and SVBAS (n=30); Group 2 - children with SVBAS without RB (n=30); Group 3 - children with RB without SVBAS (n=30). In the Group 1, compared with the 2nd and 3rd, there was an increase in the children number with high serum content of substance P (by 66.7% and 50.0%, respectively, p<0.05) and ET -1 (by 23.3% and 40.0%, respectively, p<0.05), low content of VIP (by 46.7% and 23.4%, respectively, p<0.05). Children with RB and SVBAS have serum level imbalance of the pro-inflammatory substance P, ET-1 and anti-inflammatory VIP as the bronchitis severe course basis.
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PMID:[SERUM CONTENTS OF SUBSTANCE P, ENDOTHELIN-1 AND VASOACTIVE INTESTINAL PEPTIDE IN CHILDREN WITH RECURRENT BRONCHITIS AND VERTEBROBASILAR INSUFFICIENCY]. 3132 14