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)

Nedocromil sodium is a new chemical entity. This compound is very hydrophilic and is well absorbed by tissues such as the lung but not by tissues with tight junctions such as the gut. This product is chemically different from all drugs currently used for the treatment of airway diseases. The in vitro effects of nedocromil sodium are reviewed. Nedocromil sodium is capable of blocking: 1) the chemotaxis of neutrophils; 2) the activation of macrophages and monocytes by IgE; 3) the release of histamine from mast cells; 4) the cytotoxicity of platelets; 5) the release of LTC4 from eosinophils. Nedocromil sodium thus seems to have an effect on each of the cells which are implicated in the allergic reactions. In animals, nedocromil sodium can block the immediate bronchoconstriction induced by an antigen, adenosine and neurokinin A. Nedocromil sodium can also block the increase in bronchial responsiveness induced by antigen exposure. Moreover, vascular permeability induced by ovalbumin is reduced by nedocromil sodium. In summary, nedocromil sodium demonstrated a significant inhibitory effect of inflammation in both in vivo and in vitro models.
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PMID:[Basic research on nedocromil sodium]. 131 52

We compared histamine release induced by substance P with those obtained with classical secretagogues on human basophils, lung and skin fragments. We also tested the capacity of nedocromil sodium and theophylline to inhibit histamine release in these 3 experimental models. Substance P (10(-4) M) caused a noncytotoxic histamine release (about 10% of total) from basophils, lung and skin fragments. Substance P-induced histamine release was always smaller than that obtained with optimal doses of anti-IgE, formyl-methionine phenylalanine or compound 48/80. Nedocromil sodium did not prevent secretagogue-induced histamine release from basophils or sliced skin. In contrast, it significantly inhibited anti-IgE- or substance P-induced histamine release from human lung. Theophylline caused a dose-related inhibition on these 3 models. We conclude that substance P is a modest secretagogue for human basophils and mast cells, and that skin and lung mast cells are heterogeneous with respect to their response to nedocromil sodium.
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PMID:Substance P-induced histamine release from human basophils, skin and lung fragments: effect of nedocromil sodium and theophylline. 170

1. Sensory neuropeptides such as substance P may be implicated in the pathophysiology of asthma. 2. It has been proposed that nedocromil sodium may inhibit the effects of neuropeptides. 3. In this study, using an isolated innervated preparation of rabbit trachea, substance P, 10(-6) M, potentiated contractions induced by parasympathetic stimulation. The effect of substance P at the preganglionic site (307 +/- 38% of control, n = 5), was similar to that at the postganglionic site (307 +/- 61% of control, n = 5). 4. Nedocromil sodium, 10(-7) M, significantly inhibited the substance P-induced potentiation preganglionically (199 +/- 44%, n = 4, P less than 0.05) but not postganglionically (356 +/- 118%, n = 4). 5. These results suggest that nedocromil sodium may modify neuropeptide action selectively at a preganglionic site and that this may contribute to its therapeutic efficacy.
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PMID:Nedocromil sodium inhibits substance P-induced potentiation of cholinergic neural responses in the isolated innervated rabbit trachea. 171 86

Purines and neuropeptides may act as neurotransmitters of the local axon reflex in the airways. Nedocromil sodium has been shown to inhibit adenosine- and neurokinin A-induced bronchoconstriction both in the rat and in man. In this study we used the rat model for further investigation of the mechanism of action of nedocromil sodium in the adenosine- and neurokinin A-challenge. The animals were challenged intravenously, and immediately after maximal bronchoconstriction a bronchoalveolar lavage was performed and histamine was assayed in the supernatant of the lavage fluid. Nedocromil sodium significantly inhibited the adenosine- and the neurokinin A-induced increase in histamine concentration in the lavage fluid. Nedocromil sodium had no influence on the airway responsiveness to serotonin or carbachol. We therefore concluded that the inhibitory effect of nedocromil sodium on adenosine- and neurokinin A-induced bronchoconstriction can be explained by its activity on airway mast cells.
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PMID:Effect of nedocromil sodium on bronchoconstriction induced by adenosine and tachykinins. 247 31

We characterized plasma exudation induced by direct inhalation of cigarette smoke in anesthetized, artificially ventilated guinea pigs, using Evans blue dye as a plasma marker, and investigated the neurogenic mechanisms underlying the response. Cigarette smoke increased plasma exudation in the lower trachea, main bronchi, and proximal intrapulmonary airways in a dose-related manner. Exudation was rapid in onset and was maintained for 0.5 to 2 h, depending upon airway level. Exudation was not reduced after removal of the particular phase of the smoke, nor by atropine, phentolamine, propranolol, hexamethonium, antihistamines, or bilateral vagotomy. Nicotine, at a dose calculated to approximate that in the plasma of cigarette-exposed animals, did not increase airway plasma exudation. Cigarette smoke-induce exudation was blocked by capaicinization or by a substance P antagonist and was potentiated by phosphoramidon but not by captopril. Nedocromil sodium or morphine (0.1 mg/kg each intravenously) partially inhibited cigarette smoke-induced exudation but had no effect on the response to substance P. Inhibition by morphine, but not that by nedocromil sodium, was reversed by naloxone. Thus, direct inhalation of cigarette smoke induces a dose-related, long-lasting increase in airway plasma exudation that is due to vapor-phase activation of sensory-efferent nerves, release of sensory neuropeptides that mediate the exudative response via interaction with substance P receptors, and regulation by neutral endopeptidase. The inhibitory effect of nedocromil and morphine on cigarette smoke-induced airway plasma exudation occurs through inhibition of neurotransmission.
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PMID:Mechanisms and modulation of airway plasma exudation after direct inhalation of cigarette smoke. 776 17

Evidence shows that nedocromil sodium has a major inhibitory effect on sensory nerve activation. Animal models in which inhibitory effects have been demonstrated include bradykinin- or ovalbumin-induced plasma extravasation; cigarette smoke- or sulfur dioxide-induced bronchial hyperresponsiveness and increase in inflammatory cells in the airway; and bradykinin-induced airway vasodilatation and nasal mucosal edema. Nedocromil sodium has prevented the edema in human skin induced by substance P and neurokinin A, and, in the isolated rabbit trachea, has prevented substance P-induced potentiation of cholinergic neural responses at preganglionic (but not postganglionic) sites. In vitro, the drug also has inhibited nonadrenergic noncholinergic bronchoconstriction in guinea pig bronchi. Although a protective effect against citric acid-induced cough in the dog has been reported, no data are available from models of enhanced cough reflex, such as that in asthma. Inhibition of sensory nerve activation and prevention of tachykinin release by nedocromil sodium probably contribute to its beneficial effects in the treatment of asthma.
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PMID:Effects of nedocromil sodium on airway neurogenic mechanisms. 893 86

Although sensory nerve activity may be important to the human airway in numerous possible ways, the relevance of "neurogenic inflammation" to the onset and development of asthma is unknown. However, several of the symptoms of asthma (bronchoconstriction, cough, and dyspnea) have a neuronal component that can be modeled in the laboratory by various stimuli that are thought to invoke sensory nerve activation. Nedocromil sodium is highly effective against bronchoconstriction induced by bradykinin, the tachykinins substance P and neurokinin A, and sulfur dioxide and metabisulfite. The results for induced cough in healthy subjects are equivocal, although the drug is effective on spontaneously occurring cough in patients with asthma. Nedocromil sodium had a modest but significant effect on symptoms associated with episodes of viral infection.
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PMID:Clinical effects of nedocromil sodium on challenges invoking neuronal mechanisms and on virally induced symptoms. 893 89

Nedocromil sodium (NS) and sodium cromoglycate (CS) (both applied locally into the conjunctival sac) reduced in a dose dependent manner plasma extravasation induced by topical bradykinin and by topical substance P (SP), NS being approximately ten times more potent than CS. Plasma extravasation induced by SP was unaffected by the histamine H(1) receptor antagonist, pyrilamine, which completely blocked the plasma extravasation induced by histamine. NS and CS reduced the plasma extravasation caused by the mechanical stimulation of the conjunctiva, a response that was not affected by the tachykinin NK(1) antagonist CP-(99.994). NS or CS did not affect the contraction of strips of the guinea-pig trachea in vitro caused by SP in the presence of the tachykinin NK(2) receptor antagonist SR-(48968). NS, more potently than CS, reduces the plasma extravasation caused by various inflammatory stimuli in the guinea-pig conjunctiva, without inhibiting tachykinin NK(1) receptors, but probably by acting at the level of the venular endothelium. However, an inhibitory action of NS and CS on neural transmission of sensory nerves cannot be excluded.
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PMID:Nedocromil sodium and sodium cromoglycate inhibit plasma extravasation in the guinea-pig conjunctiva. 2282 30