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 33-year-old albinotic woman whose parents were consanguineous was referred to our hospital with dry cough, dyspnea on exertion, and diffuse reticulonodular shadows on chest X-ray film. She had no apparent bleeding diathesis, although platelet serotonin content and ATP release were reduced. Open lung biopsy revealed pulmonary interstitial fibrosis with deposition of ceroid-like material with alveolar and interstitial macrophages. From these findings, the diagnosis of Hermansky-Pudlak syndrome (HPS) with interstitial pneumonia was mode. The reported characteristics of pulmonary interstitial pneumonia associated with HPS are occurrence of this disease in the thirties to forties, diffuse reticulonodular shadows in all lung fields with sparing of the subpleural zones, and bullous formation in the upper lobes. Progression usually occurs to diffuse interstitial fibrosis, but these is little decrease in lung volume. The prognosis of HPS with interstitial pneumonia is worse than that of uncomplicated HPS, and patients die of respiratory failure within 1 to 6 years after diagnosis. Steroid therapy is not effective.
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PMID:[Pulmonary interstitial pneumonia in association with Hermansky-Pudlak syndrome]. 180 83

The airway secretions which line the respiratory tract form a biphasic layer composed of an aqueous 'sol' layer and a more superficial 'gel' layer. In the sol layer, also described as the 'periciliary' layer or 'airway surface fluid', the cilia beat and relax. The lubricant sol layer enables the gel mucus present at the tips of the cilia to be transported by the ciliary beating of the ciliated cells. Due to difficulties with sampling, little is known about the physical and biochemical properties of the sol layer. The gel layer is composed of high molecular weight glycoproteins (mucins) linked with proteins and lipids. They form a gel network with a high water content (95%) and rheologic and physical properties (viscoelasticity, adhesivity) adapted in normal conditions to protect the airway mucosa, particularly through mucociliary transport. The adhesive properties of mucus, which are influenced by its lipid composition and degree of hydration, are very important in controlling the efficacy of mucus transport through ciliary activity and coughing. An intermediate viscosity and elasticity is required for optimal mucociliary transport. In obstructive airway diseases, either of genetic origin, such as cystic fibrosis (CF), or acquired (acute or chronic bronchitis), and particularly during inflammatory and infectious episodes, mucus dehydration is associated with an increase in secreted or transudated molecules and with marked augmentation of DNA content. These abnormalities contribute to the increased viscosity and adhesivity of the airway secretions and are responsible for their abnormally low transport rate by ciliary activity and for inefficient cough clearance. In view of these alterations in the physical and functional properties of CF airway secretions, pharmacologic approaches should aim to rehydrate the mucus and to restore normal mucociliary or cough transport by stimulating chloride ion secretion (i.e. using UTP or ATP associated with amiloride in order to block sodium ion and water reabsorption). During acute episodes of infection, recombinant human DNase (rhDNase) may rapidly prevent mucus stasis by improving its rheologic properties. Lubrication of the mucus at the sol phase interface by 'surfactant' therapy may also represent a very promising therapeutic perspective to reduce the hyperviscosity and hyperadhesivity of airway secretions.
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PMID:Physical and functional properties of airway secretions in cystic fibrosis--therapeutic approaches. 779 36

The ventilatory muscles perform various functions such as ventilation of the lungs, postural stabilization, and expulsive maneuvers (e.g., coughing). They are classified in functional terms as inspiratory muscles, which include the diaphragm, parasternal intercostal, external intercostal, scalene, and sternocleidomastoid muscles; and expiratory muscles, which include the abdominal muscles, internal intercostal, and triangularis sterni. The ventilatory muscles require high-energy phosphate compounds such as ATP to fuel the biochemical and physical processes of contraction and relaxation. Maintaining adequate intracellular concentrations of these compounds depends on adequate intracellular substrate levels and delivery of these substrates by arterial blood flow. In addition to the delivery of substrates, blood flow influences muscle function through the removal of metabolic by-products, which, if accumulated, could exert negative effects on several excitatory and contractile processes. Skeletal muscle substrate utilization is also dependent on the ability to extract substrates from arterial blood, which, in turn, is accomplished by increasing the total number of perfused capillaries. It follows that matching perfusion to metabolic demands is critical for the maintenance of normal muscle contractile function. In this article, I review the factors that influence ventilatory muscle blood flow. Major emphasis is placed on the diaphragm because a large number of published reports deal with diaphragmatic blood flow. The second reason for focusing on the diaphragm is because it is the largest and most important inspiratory muscle.
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PMID:Regulation of ventilatory muscle blood flow. 890 53

The antihypertensive and cough suppressant mechanisms of DU-1777 ((2S,3aS,7aS)-1-(N2-nicotinoyl-L-lsyl-gamma-D-glutamyl )octahydro-1H-indole-2 -carboxylic acid, CAS 116662-73-8), a new long-acting angiotensin-1-converting enzyme (ACE) inhibitor, were investigated in vivo and in vitro. The antihypertensive effects of DU-1777 at 10 mg/kg p.o. and cromakalim at 0.3 mg/kg p.o. were partially (about 60%) or fully antagonized by glibenclamide at 10 mg/kg i.v. in 2-kidney, 1-clip renal hypertensive rats (2K-1C RHR). The antihypertensive effects of a Ca blocker (nifedipine) and other ACE inhibitors (captopril, alacepril, enalapril, lisinopril, imidapril and quanapril) were not antagonized by glibenclamide. In deoxycorticosterone acetate-salt hypertensive rats (DOCA-HR), the antihypertensive effects of DU-1777 at 3-30 mg/kg p.o. were fully antagonized by glibenclamide. However, in vitro, DU-1777 (10(-6)-10(-3) mol/l) did not affect aortic ring contractions induced by high K (30 mmol/l). In guinea pig, citric acid induced cough was increased by ACE inhibitors, captopril, alacepril, enalapril and lisinopril (10 and 30 mg/kg p.o.). DU-1777 had a tendency to decrease citric acid induced cough and the effect was antagonized by glibenclamide. These results suggest that while DU-1777 itself does not open ATP-dependent K channel, it indirectly produces these effects through unknown mechanisms in vivo. Moreover, these effects contributed to the antihypertensive effect in DOCA-HR and cough suppressant effect in guinea pigs.
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PMID:Possible involvement of ATP-dependent K-channel related mechanisms in the antihypertensive and cough suppressant effects of the novel ACE inhibitor (2S, 3aS, 7aS)-1-(N2-nicotinoyl-L-lysyl-gamma-D-glutamyl)octahydro-1H- indole-2-carboxylic acid. 923 50

The effect of the K(ATP) channel openers, pinacidil and cromakalim, on coughing was studied in guinea pigs exposed to a nebulized aqueous solution of citric acid (0.50 M). Both pinacidil and cromakalim, subcutaneously administered 45 min before the test, inhibited coughing. The D50 (95% CI) were 0.95 +/- 0.90 mg/kg for cromakalim and 3.25 +/- 0.92 mg/kg for pinacidil. Under our experimental conditions, the D50 (95% CI) of codeine was 1.74 +/- 0.75 mg/kg. The combination of cromakalim and pinacidil with codeine produced an additive effect. An additive effect was also produced by the combination of pinacidil with the selective tachykinin NK2 receptor antagonist MEN 10,627 = [cyclo(Met-Asp-Trp-Phe-Dap-Leu)cyclo(2beta-5beta)]. The antitussive effect of pinacidil and cromakalim was not a consequence of a bronchodilating effect, which was absent at these dose levels under our experimental conditions. These results indicate that K(ATP) channel openers have an opioid-like antitussive effect and may suggest a novel approach to the symptomatic treatment of coughing.
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PMID:Antitussive effect of K+ channel openers. 1035 92

Several reports have demonstrated that the number of capsaicin-induced coughs is increased in the presence of prostaglandins in the airway. Moreover, it has been reported that the expression of cyclooxygenase-2, which converts arachidonic acid to prostaglandins, was found in cultured human airway epithelial cells in the absence of inflammatory cytokine stimulation. Thus, it is possible that cyclooxygenase-2 inhibitor may produce an antitussive effect. To test this hypothesis, we investigated the effects of N-[2-(cyclohexyloxy)-4-nitrofenyl]-methane sulfonamide (NS-398), a selective cyclooxygenase-2 inhibitor, and 5-(4-chlorophenyl)-1-(4-methoxyphenyl)-3-trifluoromethyl-pyrazole (SC-560), a selective cyclooxygenase-1 inhibitor, on capsaicin-induced coughs in guinea pigs. NS-398 (1-10 mg/kg, p.o.) dose-dependently and significantly reduced the number of capsaicin-induced coughs. In contrast, SC-560 (10 mg/kg, p.o.) did not reduce the number of capsaicin-induced coughs. The antitussive effect of NS-398 (10 mg/kg, p.o.) was not antagonized by pretreatment with methysergide (3 mg/kg, i.p.), a non-selective serotonin (5-HT) receptor antagonist, or glibenclamide (10 mg/kg, i.p.), an ATP-sensitive K(+) channel blocker. Furthermore, although NS-398 did not significantly affect the cough reflex induced by substance P (10(-16) M), it significantly reduced the capsaicin-induced release of substance P in bronchoalveolar lavage fluid (BALF). The present findings clearly show that cyclooxygenase-2 inhibitor, but not cyclooxygenasez-1 inhibitor, has a potent antitussive effect. Furthermore, it is possible that the antitussive action of NS-398 does not depend on centrally acting mechanisms, since 5-HT receptors play an important role in the cough-depressant activities of centrally acting antitussive drugs. NS-398 may exert peripheral antitussive effects by inhibiting the release of substance P from capsaicin-sensitive afferent C-fibers in the airways. These results suggest that cyclooxygenase-2 inhibitors may have a therapeutic benefit in reducing coughs.
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PMID:Antitussive effect of NS-398, a selective cyclooxygenase-2 inhibitor, in guinea pigs. 1530 9

There are several receptors capable of inducing activating generator potentials in cough-associated afferent terminals in the airways. The chemical receptors leading to generator potentials can be subclassified into ionotropic and metabotropic types. An ionotropic receptor has an agonist-binding domain, and also serves directly as an ion channel that is opened upon binding of the agonist. Examples of ionotropic receptors found in airway sensory nerve terminals include receptors for serotonin (5-HT3 receptors), ATP (P2X receptors), acetylcholine (nicotinic receptors), receptors for capsaicin and related vanilloids (TRPV1 receptors), and acid receptors (acid sensing ion channels). Afferent nerve terminals can also be depolarized via activation of metabotropic or G-protein coupled receptors (GPCRs). Among the GPCRs that can lead to activation of airway afferent fibers include bradykinin B2 and adenosine A1 receptors. The signaling events leading to GPCR-mediated membrane depolarization are more complex than that seen with ionotropic receptors. The GPCR-mediated effects are thought to occur through classical second messenger systems such as activation of phospholipase C. This may lead to membrane depolarization through interaction with specific ionotropic receptors (such as TRPV1) and/or various types of calcium activated channels.
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PMID:Ionotropic and metabotropic receptor mediated airway sensory nerve activation. 1556 76

We examined the effect of inhaled ATP on the chemical irritant-induced coughs to clarify the roles of ionotropic purinergic receptors in these modulations. Although inhalation of 0.1 M citric acid by itself produced only a few coughs in guinea pigs, exposure to ATP, at concentrations of 3-10 microM, for 2 min concentration-dependently increased the number of 0.1 M citric acid-induced coughs. ATP-induced enhancement of the number of citric acid-induced coughs was abolished when animals were pretreated with 2',3'-O-(2,4,6-trinitrophenyl) adenosine 5-triphosphate (TNP-ATP), an antagonist of P2X receptor subtypes P2X1-4, at a concentration of 50 microM, for 2 min. However, exposure to pyridoxal-phosphate-6-azophenyl-2',4'-disulphonic acid (PPADS), an antagonist of P2X receptor subtypes P2X1,2,3,5,7, but not of P2X4 receptors, at a concentration of 50 microM, for 2 min, had no effect on the ATP-induced enhancement of the number of citric acid-induced coughs. Furthermore, exposure to reactive blue 2 (RB2, 30 microM, 2 min), an antagonist of P2Y receptors, had no effect on the ATP-induced enhancement of the number of citric acid-induced coughs. Exposure to ATP, at a concentration of 10 microM, for 2 min significantly increased the number of citric acid-induced coughs in capsaicin-pretreated guinea pigs. Furthermore, ATP had no effect on the number of capsaicin-induced coughs in naive animals. These results suggest that although ATP, by itself, does not elicit spontaneous coughs, it likely enhances the cough reflex sensitivity. Furthermore, stimulation of P2X receptors, especially P2X4 receptors, on rapidly adapting receptors may be required for the ATP-induced enhancement of the cough reflex sensitivity.
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PMID:Involvement of P2X receptor subtypes in ATP-induced enhancement of the cough reflex sensitivity. 1632 75

We examined the effect of inhaled histamine on citric acid-induced coughs and clarified the role of ionotropic purinergic receptors in the resulting changes. Although the inhalation of 0.1 M citric acid by itself produced only a few coughs in guinea pigs, exposure to histamine, at concentrations of 0.3 to 1 mM, for 2 min concentration dependently increased the number of citric acid-induced coughs. This histamine-induced increase in the number of citric acid-induced coughs was dose dependently and significantly reduced when animals were pretreated with fexofenadine, a histamine H1 receptor antagonist. The histamine-induced increase in the number of citric acid-induced coughs was completely reduced when animals were co-pretreated with 2',3'-O-(2,4,6-trinitrophenyl) adenosine 5-triphosphate (TNP-ATP, 50 microM), a P2X receptor antagonist, and reactive blue 2, a P2Y receptor antagonist, for 2 min. Furthermore, the ATP-induced increase in the number of citric acid-induced coughs was dose dependently and significantly decreased when animals were pretreated with fexofenadine, at doses of 0.3, 1 and 3 mg/kg, p.o. These results suggest that histamine enhances the excitability of rapidly adapting receptors to tussive stimuli via modulation of ATP release in the airways. Furthermore, ATP might act not only on P2X receptors to directly activate rapidly adapting receptors, but also on P2Y receptors to increase histamine release, indirectly increasing the cough reflex sensitivity.
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PMID:Involvement of ionotropic purinergic receptors in the histamine-induced enhancement of the cough reflex sensitivity in guinea pigs. 1693 79

One of the main functions of the airway epithelium is to inactivate and remove infectious particles from inhaled air and thereby prevent infection of the distal lung. This function is achieved by mucociliary and cough clearance and by antimicrobial factors present in the airway surface liquid (ASL). There are indications that airway defenses are affected by the pH of the ASL and historically, acidification of the airway surfaces has been suggested as a measure of airway disease. However, even in health, the ASL is slightly acidic, and this acidity might be part of normal airway defense. Only recently research has focused on the mechanisms responsible for acid and base secretion into the ASL. Advances resulted from research into the airway disease associated with cystic fibrosis (CF) after it was found that the CFTR Cl(-) channel conducts HCO (3) (-) and, therefore, may contribute to ASL pH. However, the acidity of the ASL indicated parallel mechanisms for H(+) secretion. Recent investigations identified several H(+) transporters in the apical membrane of the airway epithelium. These include H(+) channels and ATP-driven H(+) pumps, including a non-gastric isoform of the H(+)-K(+) ATPase and a vacuolar-type H(+) ATPase. Current knowledge of acid and base transporters and their potential roles in airway mucosal pH regulation is reviewed here.
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PMID:Mechanisms of acid and base secretion by the airway epithelium. 1709 Dec 14


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