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)

Intratracheal instillation of Sephadex beads induced a long-lasting inflammation in the rat lung as seen by an increase in lung weights. Repeated instillation enhanced this reaction and increased lung endothelin-1 content 3.5 times. Budesonide given s.c. abolished these effects and even reduced basal endothelin-1 content by 72%. The tissue content of the sensory neuropeptide neurokinin A were unaffected by both treatments. Endothelin has been proposed to play a part in the pathogenesis of bronchial asthma. If it is so, the ability of budesonide to reduce endothelin-1 content could thus be added to the list of beneficial effects of glucocorticosteroids in these conditions.
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PMID:Regulation of lung endothelin content by the glucocorticosteroid budesonide. 128 Jan 29

Neurokinin A (NKA) has been shown to exert a potent contractile action on bronchial smooth muscles both in vitro and in vivo. Although this effect seems to be due either to a direct action of this peptide on specific muscular receptors or to an indirect effect on mast cells and/or nerves, its mechanism of action in bronchial asthma is still unknown. In the present study we have investigated the airway response to inhaled NKA in 10 asthmatic subjects and the activity of the novel pyranoquinoline dicarboxylic acid drug, nedocromil sodium, on this response. Ten asthmatic patients with stable asthma took part in the study consisting of four separate visits. On the first two occasions we derived histamine and NKA PD15 values in absence of any drug treatment. On the following two visits the inhalation challenge with NKA was performed after administration of either nedocromil sodium or matched placebo administered as pressurized aerosols via metered dose inhalers in a randomized double-blind order. Inhaled NKA produced a dose-related fall in FEV1 in all the subjects studied. Inhaled nedocromil sodium had a significant effect on the FEV1 response to NKA inhalation, the geometric mean PD15 value increasing from 16.6 to 32.2 x 10(-9) mol. We conclude that nedocromil sodium attenuates subsequent responsiveness to inhaled NKA in asthmatic subjects.
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PMID:Protection of nedocromil sodium on bronchoconstriction induced by inhaled neurokinin A (NKA) in asthmatic patients. 131 88

Neuropeptides such as neurokinin A (NKA) have been proposed as important mediators of bronchoconstriction and airway hyperresponsiveness in asthma. Inhaled NKA causes bronchoconstriction in patients with asthma, but not in normal subjects. This is possibly due to the activity of an endogenous neuropeptide-degrading enzyme: neutral endopeptidase (NEP). We investigated whether a NEP-inhibitor, thiorphan, reveals bronchoconstriction to NKA or NKA-induced changes in airway responsiveness to methacholine in normal humans in vivo. Eight normal male subjects participated in a double-blind crossover study, using thiorphan as pretreatment to NKA challenge. Dose-response curves to inhaled NKA (8 to 1,000 micrograms/ml, 0.5 ml/dose) were recorded on 2 randomized days 1 wk apart, and methacholine tests were performed 48 h before and 24 h after the NKA challenge. Ten minutes prior to NKA challenge the subjects inhaled either thiorphan (2.5 mg/ml, 0.5 ml) or placebo. To detect a possible nonspecific effect of thiorphan, we investigated the effect of the same pretreatment with thiorphan or placebo on the dose-response curve to methacholine in a separate set of experiments. The response was measured by the flow from standardized partial expiratory flow-volume curves (V40p), expressed in percent fall from baseline. NKA log dose-response curves were analyzed using the area under the curve (AUC) and the response to the highest dose of 1,000 micrograms/ml (V40p,1000). The methacholine dose-response curves were characterized by their position (PC40V40p) and the maximal-response plateau (MV40p). Baseline V40p was not affected by either pretreatment (p greater than 0.15).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The effect of an inhaled neutral endopeptidase inhibitor, thiorphan, on airway responses to neurokinin A in normal humans in vivo. 131 91

The release of neurotransmitters may exacerbate the inflammatory response. Such neurogenic inflammation has been documented in a number of inflammatory diseases. Neurogenic inflammation due to release of neuropeptides from sensory nerves has been demonstrated in airways of several species, particularly rodents, and may contribute to the inflammatory response in asthmatic airways. Tachykinins (substance P and neurokinin A) released from airway sensory nerves may cause bronchoconstriction, vasodilatation, plasma exudation, and mucus secretion, whereas another sensory neuropeptide, calcitonin generelated peptide, may contribute to hyperemia of inflammation. Airway epithelial damage in asthma exposes sensory nerves which may become sensitized by inflammatory products (including prostaglandins and cytokines) so that neuropeptides are released via a local reflex trigger such as bradykinin, resulting in exaggerated inflammation. The effects of tachykinins may be amplified further by loss of the major degrading enzyme, neutral endopeptidase, from epithelial cells. Direct evidence for neurogenic inflammation in asthma is still awaited, however. Several strategies for reducing neurogenic inflammation are possible, particularly inhibition of neuropeptide release from sensory nerves by stimulating prejunctional receptors such as mu-opioid receptors.
J Asthma 1992
PMID:Neurogenic inflammation and asthma. 135 Oct 52

Neural control of the airways may be abnormal in asthma and neurogenic mechanisms may contribute to the pathophysiology of asthma. Cholinergic nerves are the predominant bronchoconstrictor pathway in airways and cholinergic neurotransmission may be increased in asthma by the effects of inflammatory mediators on afferent nerves (reflex effect) and on prejunctional receptors on postganglionic nerves. In addition there may be a defect in prejunctional M2-receptors on cholinergic nerves resulting in increased cholinergic neural effects. beta-Adrenoceptor function may be abnormal in asthmatic airways as a result of chronic inflammation, but alpha-receptors are probably unimportant in regulation of human airway tone. Inhibitory NANC nerves are the only bronchodilator pathway in human airways, and there is some evidence that the neurotransmitter is predominantly nitric oxide, although vasoactive intestinal peptide may be contributory. It is possible that i-NANC function may be abnormal in asthma as a consequence of inflammation. Unmyelinated sensory nerves contain a variety of potent inflammatory peptides, including substance P and neurokinin A, which might be released in chronic inflammation, particularly if there is a proliferation of these nerves, increased neuropeptide synthesis or reduced metabolism by neutral endopeptidase.
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PMID:Neural mechanisms in asthma. 135 67

Several new drugs are now under development for the treatment of asthma, either as improvements to existing classes of therapy or as novel agents. Amongst bronchodilators, long-acting inhaled beta 2-agonists (salmeterol and formoterol) look very promising and there is also interest in selective phosphodiesterase inhibitors, K+ channel-openers and nitrodilators. There are several new inhaled corticosteroids under development and more selective agents include leukotriene antagonists, 5-lipoxygenase inhibitors, bradykinin and tachykinin antagonists and immunomodulators. In the future, adhesion molecule inhibitors and cytokine inhibitors may be developed.
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PMID:New drugs for asthma. 135 72

Axon reflex mechanisms may be involved in the pathogenesis of asthma, but there has been no direct evidence that endogenous tachykinins cause bronchoconstriction in asthmatic subjects. We have studied the effect of a tachykinin receptor antagonist (FK-224) on bronchoconstriction induced by inhalation of bradykinin in asthmatic patients. In a double-blind, placebo-controlled, crossover trial, ten subjects with stable asthma were given FK-224 (4 mg) or placebo by inhalation 20 min before challenge with bradykinin (0-1250 micrograms/ml, five breaths of each concentration) given with 5 min intervals. Bradykinin caused dose-dependent bronchoconstriction in all subjects. FK-224 significantly opposed the bronchoconstrictor effect; the geometric mean of the cumulative concentration required to elicit a 35% fall in specific airway conductance was 5.3 micrograms/ml after placebo and 40 micrograms/ml after FK-224 (p < 0.001). Inhalation of bradykinin caused coughing in three subjects, which was inhibited by FK-224 in all three. Antagonism of the tachykinin receptor by FK-224 greatly inhibited both bronchoconstriction and coughing induced by bradykinin in asthmatic patients, suggesting that tachykinin release from the airway sensory nerves is involved in responses to bradykinin. Tachykinin receptor antagonists may be useful in the treatment of asthma.
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PMID:Protection against bradykinin-induced bronchoconstriction in asthmatic patients by neurokinin receptor antagonist. 135 19

The aim of the present study was to examine whether endogenous neuropeptides released from sensory nerves can potentiate airway responsiveness to histamine. Total pulmonary resistance (RL) was measured to assess the bronchial responsiveness to increasing doses of histamine (1.25, 2.5, 5, and 10 micrograms/kg) administered intravenously in 29 anesthetized and artificially ventilated guinea pigs. Pretreatment with aerosolized capsaicin (3 micrograms/ml for 15 to 60 s) 30 min before obtaining the dose-response to histamine significantly potentiated percent increase in RL caused by each dose of intravenously administered histamine. Pretreatment with substance P (0.5 ml/kg of 10(-5) M) administered intravenously also potentiated the airway responsiveness to histamine. As assessed by the amount of extravasation of Monastral blue pigments, both capsaicin aerosol and substance P injected intravenously induced increased vascular permeability in the tracheal mucosa. These findings suggest that endogenous neuropeptides, especially tachykinin such as substance P, can induce airway hyperresponsiveness to nonspecific stimuli and play a possible role in producing airway hyperresponsiveness in bronchial asthma.
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PMID:Pretreatment with aerosolized capsaicin potentiates histamine-induced bronchoconstriction in guinea pigs. 137 54

Substance P is a decapeptide which forms part of the group known as neuropeptides, that is, peptides released by some neurones such as the slow-conducting C fibres and the rapid-conducting A-delta fibres. These neurones belong to the category of non-adrenergic non-cholinergic nerves (NANC), which perform their action through a mechanism known as "axonic reflex". This mechanism is an antidromic stimulation which produces a secretion of neuropeptides, especially substance P. It is known that substance P, once released, is able to exert a number of actions including among others inflammatory and bronchospastic activities and a stimulation of the immunologic system. Other effects attributed to this substance are an increase in capillary permeability and oedema and the perpetuation of certain conditions such as asthma, rhinitis and chronic urticaria or hives. The production, metabolism and actions of this neuropeptide are described.
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PMID:[Substance P: immuno-allergic implications]. 138 Jul 67

Data from several studies suggest that tachykinins may play an important role in the pathophysiology of airway diseases, especially asthma. Our aim is to discover tachykinin antagonists which exhibit therapeutically useful anti-asthmatic activity. In our search for activities inhibiting the binding of [3H]substance P to guinea-pig lung membrane preparations, we have found that the fermentation product, WS9326A, isolated from Streptomyces violaceusniger, is a potent tachykinin receptor antagonist.
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PMID:WS9326A, a novel tachykinin antagonist isolated from Streptomyces violaceusniger no. 9326. I. Taxonomy, fermentation, isolation, physico-chemical properties and biological activities. 138 43


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