Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0010200 (cough)
 23,843 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A noncholinergic, nonadrenergic nervous system has been described, involving the sensory nerves in the airways. Chemicals, dusts and other irritants stimulate these sensory nerves to release substance P and related neuropeptides. These neuropeptides have the remarkable ability to affect multiple cells in the airways and to provoke many responses including cough, mucus secretion, smooth muscle contraction, plasma extravasation and neutrophil adhesion. This series of effects is termed "neurogenic inflammation." An enzyme exists on the surfaces of all lung cells that contain receptors for these neuropeptides. This enzyme, neutral endopeptidase (NEP), by cleaving and thus inactivating the neuropeptides, limits the concentration of the neuropeptide that reaches the receptor on the cell surface. Thus, neurogenic inflammatory responses are normally mild and presumably protective in nature. However, when NEP is inhibited pharmacologically (with NEP inhibitors) or by cigarette smoke, respiratory viral infection, or by inhalation of the industrial pollutant toluene diisocyanate, neurogenic inflammatory responses are exaggerated. Delivery of exogenous human recombinant NEP inhibits neurogenic inflammation. Finally, evidence is provided that corticosteroids suppress neurogenic plasma extravasation and that this drug can upregulate NEP in human airway tissue. Neutral endopeptidase cleaves multiple peptides. Thus, its selectivity resides, at least in part, on its fixed location on the surfaces of specific cells where it can modulate effects of peptides exposed to the cells' surfaces.
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PMID:Neutral endopeptidase modulates neurogenic inflammation. 188 1

The enzyme neutral endopeptidase (NEP) is bound to the membranes of selected cells in the airways that have receptors for tachykinins. The location of the enzyme, along with its selectivity of substrates (tachykinins are a preferred substrate), allows the enzyme to cleave tachykinins that come close to the cell-surface receptors. By cleaving and thus inactivating tachykinins released during stimulation of the sensory nerves, NEP limits the degree of neurogenic inflammation. Neutral endopeptidase exists in the basal cells of the airway epithelium, nerves, smooth muscle, glands, blood vessels, and perhaps other cells. Thus, the enzyme modulates smooth muscle contraction, gland secretion, cough, vascular permeability, and neutrophil adhesion. Decreased NEP activity occurs with epithelial removal, during respiratory viral infections, and during exposure to irritants (e.g., cigarette smoke and toluene diisocyanate). Delivery of recombinant NEP (rNEP) by aerosol suppressed cough responses during neurogenic inflammation. We suggest that decreased NEP activity will result in exaggerated neurogenic inflammation and may play an important role in inflammatory diseases in airways. Furthermore, drugs that cause up-regulation of NEP may play a therapeutic role by suppressing neurogenic responses. Replacement therapy with rNEP may be useful in diseases where inflammatory peptides (e.g., tachykinins, bradykinin) play a role in pathogenesis.
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PMID:Modulation of neurogenic inflammation by neutral endopeptidase. 200 87

To determine whether recombinant enkephalinase (neutral endopeptidase, EC 3.4.24.11) prevents cough induced by exogenously applied and endogenously released neuropeptides, we measured cough responses to aerosolized solutions of substance P or of capsaicin for 2 min in random-source guinea pigs before or after exposing them to aerosolized recombinant human enkephalinase. Substance P (10(-16) M) increased coughing compared with its vehicle. Enkephalinase (120 micrograms) inhibited cough induced by subsequent exposure to substance P compared with the response to substance P alone, but after further exposure to the enkephalinase inhibitor leucine-thiorphan (10(-5) M), substance P increased cough significantly. Similar results were obtained for capsaicin-induced cough. In pathogen-free guinea pigs, after they inhaled inactive recombinant enkephalinase (33 micrograms), capsaicin (10(-13) M) increased cough significantly. In contrast, after they inhaled active recombinant enkephalinase (33 micrograms), capsaicin increased cough only slightly. These results suggest that aerosolized enkephalinase reaches the sites of release or actions of endogenous neuropeptides and, by degrading them, prevents cough induced by their release. Furthermore, these studies suggest that recombinant enkephalinase might be useful in the treatment of cough and other symptoms of diseases involving peptides cleaved by this enzyme.
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PMID:Recombinant human enkephalinase (neutral endopeptidase) prevents cough induced by tachykinins in awake guinea pigs. 247 75