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

The case of a twelve years old boy with unilateral medullary carcinoma of the thyroid gland, whose main symptoms were cough, hemoptisis, fever and weight loss is reported. The diagnosis was made by lymph node biopsy, high levels of serum calcitonin and a positive skin test for histaminase. The main clinical, anatomical and genetic features of this tumor are discussed. The familial study did not show any other affected member. Therefore, it was considered as a sporadic case. Emphasis is made on the diagnostic methodolgy.
 ...
PMID:[Medullary carcinoma of the thyroid gland. Report of a case]. 127 61

In the present study we evaluated the effects of ruthenium red, a blocker of transmembrane Ca2+ fluxes, on bronchoconstriction and the release of calcitonin gene-related peptide-like immunoreactivity induced by different stimuli in the isolated perfused guinea-pig lung. Vagal stimulation (1 Hz, 1 min), capsaicin (10(-8) M, 10(-6) M), resiniferatoxin (3 x 10(-10) M), nicotine (10(-4) M), bradykinin (5 x 10(-6) M) and histamine (10(-5) M) evoked bronchoconstriction and calcitonin gene-related peptide-like immunoreactivity overflow. Ruthenium red (5 x 10(-6) M) almost completely inhibited the bronchoconstriction and calcitonin gene-related peptide-like immunoreactivity overflow induced by capsaicin and resiniferatoxin but did not influence the effects induced by vagal nerve stimulation, nicotine, bradykinin or histamine. The 20-deacetylated derivative of resiniferatoxin (ROPA), which lacks the homovanillyl ester group, did not evoke release or bronchoconstriction. Ruthenium red (3 x 10(-4) M) aerosol attenuated the cough induced by nebulized citric acid in conscious guinea-pigs. Citric acid-induced coughing is mediated via capsaicin-sensitive neurons. However, cigarette smoke-induced coughing, which involves capsaicin-resistant mechanisms, was not affected by ruthenium red. In conclusion, ruthenium red selectively inhibits the capsaicin, resiniferatoxin and citric acid-induced excitation of the sensory nerves as revealed by calcitonin gene-related peptide-like immunoreactivity release, bronchoconstriction and coughing, suggesting that these agents share a common mechanism of action.
 ...
PMID:Selectivity of ruthenium red in inhibiting bronchoconstriction and CGRP release induced by afferent C-fibre activation in the guinea-pig lung. 171 14

Environmental pollutants may induce airway hyperresponsiveness to bronchonconstrictor stimuli, but if there is a concomitant change in other defensive reflexes, like the cough reflex, is not known. We have examined how two weeks' exposure to cigarette smoke influences airway sensitivity to inhaled irritants acting mainly through capsaicin-sensitive sensory neurons (citric acid, capsaicin) or rapidly adapting stretch receptors (cigarette smoke, histamine). Guinea-pigs were exposed, over a period of one hour, to cigarette smoke or room air, twice daily for 2 weeks. Twenty-four hours after the end of the smoke exposure coughing produced by nebulized citric acid (0.40 M) and capsaicin (30 microM) was enhanced 3.7 (P less than 0.001) and 2.5 (P less than 0.05) times, respectively, whereas the cigarette smoke-induced cough was unchanged. The enhanced responsiveness gradually returned to normal over a period of three weeks and was not mediated by cyclo-oxygenase products since it was not affected by indomethacin (3 mumols kg-1). In contrast, the broncho-constrictor responses to citric acid, capsaicin, cigarette smoke and histamine (0.70 mM) were not altered by inhalation of cigarette smoke. Smoke-exposed animals had a significantly (P less than 0.05) increased amount of calcitonin gene-related peptide-like material (CGRP, contained in capsaicin-sensitive sensory neurons) in tracheal tissue, suggesting that chronic irritation stimulates peptide synthesis. The amount of neuropeptide Y-like material (in autonomic motor nerves) in pulmonary tissue was not changed indicating some 'specificity' in the irritative effect of smoke. It is concluded that prolonged exposure to cigarette smoke produces a tussive hyperresponsiveness that seems to involve specifically capsaicin-sensitive, CGRP-containing sensory neurons mediating cough. The present data demonstrate the development of a 'sensory' hyperresponsiveness, separate from airway hyperresponsiveness to bronchoconstrictor agents.
 ...
PMID:Hyperresponsiveness to tussive stimuli in cigarette smoke-exposed guinea-pigs: a role for capsaicin-sensitive, calcitonin gene-related peptide-containing nerves. 187 46

C-fiber afferents in the airways are in close contact with mast cells and are activated both upon allergic reactions and by inhalation of irritants such as capsaicin and cigarette smoke. This evokes both protective reflexes such as cough as well as local release of tachykinins and calcitonin gene-related peptide (CGRP) with subsequent actions on blood vessels (vasodilatation and plasma protein extravasation) and bronchial smooth muscle (bronchoconstriction). After capsaicin pretreatment when peptides have been depleted from the sensory nerves, there is a marked reduction of the vasodilatatory response upon allergen challenge and the protein extravasation evoked by cigarette smoke. Conversely, chronic cigarette smoke exposure is accompanied by increased coughing to capsaicin challenge. Furthermore, aerosol immunization and chronic smoke exposure are both associated with elevated tissue levels of CGRP, suggesting upregulation of C-fiber function and peptide synthesis, which may contribute to airway hyperreactivity.
 ...
PMID:Sensory neuropeptide involvement in animal models of airway irritation and of allergen-evoked asthma. 204 32

Neural pathways involved in cough and reflex bronchoconstriction and the effects of drugs on these airway reflexes have been studied in unanaesthetised guinea-pigs exposed to aerosols of citric acid (0.13-0.78 M), capsaicin (30 microM), nicotine (9.2 mM) and histamine (0.9 mM). The number of coughs was counted during the first 3 min of exposure and the time to onset of signs of dyspnea, as an indication of bronchoconstriction, was measured. Citric acid produced bronchoconstriction and dose-dependently increased the number of coughs. Capsaicin produced both cough and bronchoconstriction. Nicotine mainly produced cough and histamine bronchoconstriction. Pretreatment of adult guinea-pigs with capsaicin (50 mg kg-1 s.c.) produced a long-lasting (greater than or equal to 10 weeks) depletion of substance P- and calcitonin gene related peptide-like immunoreactivities in the sensory nerves of the larynx, tracheobronchial tree and lung. In capsaicin-treated animals, citric acid (0.39 M) and capsaicin (30 microM) caused neither cough nor bronchoconstriction. Nicotine (9.2 mM) and mechanical stimulation still produced cough, and histamine (0.9 mM) bronchoconstriction. It is concluded that in guinea-pigs both capsaicin-sensitive (probably C-fibre endings) and capsaicin-resistant (probably rapidly adapting stretch receptors) afferent neurons may be involved in cough and reflex bronchoconstriction.
 ...
PMID:Cough and bronchoconstriction mediated by capsaicin-sensitive sensory neurons in the guinea-pig. 298 Feb 86

An isolated perfused lung model was developed in which the mechanisms of regulation of sensory neuropeptide overflow and bronchoconstrictor responses evoked by antidromic vagal nerve stimulation or various irritants could be studied. For further comparison, non-adrenergic non-cholinergic (NANC) bronchoconstriction was also studied in guinea-pig isolated bronchus and in vivo. In the isolated guinea-pig lung, spontaneous strong postmortem bronchoconstriction occurred; this had to be overcome by the beta 2-adrenoceptor agonist terbutaline. Vagal stimulation, capsaicin, resiniferatoxin (RTX), nicotine, and pH 5 buffer all caused sensory peptide release and bronchoconstriction via a capsaicin-sensitive mechanism. Bradykinin and histamine also stimulated sensory peptide release but evoked bronchoconstriction mainly via capsaicin-resistant mechanisms. Stimulation at low frequency (1 Hz) caused similar degree of sensory nerve activation (peptide release in perfused lung and NANC bronchial contraction in bronchus) as stimulation at 10 Hz. Dactinomycin and the non-peptide SR 48968 selectively blocked the bronchoconstriction induced by neurokinin 2 (NK2) receptor agonists and also depressed that induced either by vagal stimulation or capsaicin, with no prejunctional effect on the overflow of calcitonin gene-related peptide (CGRP). Furthermore, SR 48968 inhibited the bronchoconstriction to citric acid aerosol. The NK1 antagonist CP 96345 had only marginal effects on NANC bronchoconstriction. Tetrodotoxin (TTX) and omega-conotoxin (CTX) inhibited neuropeptide release and bronchoconstriction caused by vagal stimulation or a low concentration of capsaicin but only marginally attenuated the effects evoked by a high concentration of capsaicin, or nicotine. Prejunctional alpha 2-adrenoceptor or opiate receptor activation inhibited the neuropeptide release and bronchoconstriction induced by vagal stimulation or a low concentration of capsaicin. Ruthenium red had a selective inhibitory effect on the overflow of neuropeptides [CGRP, neurokinin A (NKA)] and bronchoconstriction induced by capsaicin and its analogue RTX but not on responses induced by vagal stimulation, nicotine, bradykinin and histamine. It also inhibited CGRP and NKA release and bronchoconstriction caused by pH 5 buffer in lung, as well as cough and nasal irritation provoked by citric acid in vivo. The capsaicin receptor antagonist capsazepine inhibited peptide (CGRP, NKA) release and bronchoconstriction produced by capsaicin but not that evoked by vagal stimulation, nicotine and bradykinin, suggesting selectivity. Citric acid (in vivo) and pH 5 buffer (in vitro) produced bronchoconstriction via activation of capsaicin-sensitive sensory nerves. Interestingly, capsazepine also markedly depressed peptide overflow and bronchoconstriction caused by pH 5 buffer in isolated guinea-pig lung.(ABSTRACT TRUNCATED AT 400 WORDS)
 ...
PMID:Regulation of neuropeptide release from pulmonary capsaicin-sensitive afferents in relation to bronchoconstriction. 769 42

Idiopathic persistent nonproductive cough (PNPC) is characterized by enhanced cough sensitivity to inhaled capsaicin, suggesting that capsaicin-sensitive afferent airway nerves are either present in increased numbers or functionally upregulated. In 16 patients with idiopathic PNPC and eight healthy control subjects, we measured cough sensitivity to inhaled capsaicin and the anatomic density in bronchial epithelium of nerves immunoreactive for the general nerve-marker protein gene product (PGP)-9.5 and the sensory neuropeptides calcitonin-gene-related-peptide (CGRP) and substance-P (SP). The log concentrations of capsaicin required to elicit at least two (C2) and five (C5) coughs were significantly lower in patients (P) than in control subjects (C) (median [range] log C2, P = 0.3 [-0.3 to 1.2] microM; C = 1.5 [0.9 to 2.1], p < 0.0005; log C5, P = 0.8 [-0.3 to 2.1]; C = 2.6 [1.8 to 3.0], p < 0.0005). In bronchial epithelium taken from the carina of the right upper lobe (RUL) and a subsegmental carina of the right lower lobe (RLL), total nerve density (PGP-9.5 immunoreactivity) was greater in P than C, although this was not significant. CGRP-immunoreactive nerve density was significantly higher in P than in C in the RUL (median [range] P = 1.05% [0.13 to 5.08]; C = 0.02% [0 to 0.24], p = 0.001) and RLL (P = 0.59% [0.04 to 3.14]; C = 0% [0 to 0.50], p < 0.02). SP-immunoreactive nerves were not significantly different in the two groups. Abnormal intraepithelial airway nerves containing increased quantities of CGRP are present in patients with idiopathic PNPC.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Abnormal intraepithelial airway nerves in persistent unexplained cough? 852 Jul 77

Angiotensin converting enzyme (ACE) -inhibitors inhibit degradation of inflammatory mediators substance P (SP) and bradykinin, which may further stimulate the synthesis of prostaglandins. The resulting increase in inflammatory mediators in tissues is suggested to be the reason for the dry cough, involving sensory C-fiber activation, among patients receiving ACE-inhibitor therapy. In the present study, the effect of an ACE-inhibitor, captopril, on ocular irritative responses was studied in the rabbit. Intravenous captopril decreased markedly the blood pressure and the intraocular pressure (IOP) modestly. Topical neutral formaldehyde elicits an irritative response in the eye mediated through sensory neuropeptides SP and calcitonin gene-related peptide (CGRP). Following topical neutral formaldehyde, the increase in IOP and breakdown of the blood-aqueous barrier were inhibited by captopril, while miosis was not affected. Cyclic AMP (cAMP) content in the aqueous humour was increased by captopril, and this increase was inhibited by indomethacin. Following YAG-laser anterior capsulotomy, captopril inhibited the increase in IOP, breakdown of the blood-aqueous barrier and miosis. The present study demonstrates that use of short-term administration of captopril prior to sensory nerve stimulation or YAG laser anterior capsulotomy does not enhance the ocular responses to these stimuli in the rabbit. In the present study, captopril inhibited these responses, at least partly by decreasing the blood pressure.
 ...
PMID:Effect of captopril on ocular irritative response to topical neutral formaldehyde and YAG-laser capsulotomy in the rabbit. 859 Feb 56

Asthmatic subjects cough and bronchoconstrict to various agents known to stimulate sensory nerves. A population of sensory nerves, the C fibres, contain the neuropeptides substance P, neurokinin A (NKA), and calcitonin gene-related peptide (CGRP). Capsaicin, the principal ingredient of hot peppers, selectively stimulates C fibre afferents resulting in the release of these proinflammatory peptides. An upregulation in the function of sensory nerves may lead to augmented afferent and efferent function which, in asthma, could contribute to bronchial hyper-responsiveness, inflammation, and remodelling of the airway wall. Drugs specifically designed to attenuate the function of airway sensory nerves may prove useful in the treatment of asthma.
 ...
PMID:Airway sensory nerves: a burning issue in asthma? 877 45

1. We tested the hypothesis that the pattern and the intensity of autonomic mechanisms causing vasoconstriction in the resting bronchial circulation of awake dogs also exists in awake sheep. It was also postulated that sighing behaviour and the associated bronchovascular dilatation induced by non-adrenergic, non-cholinergic (NANC) mechanisms observed in the dog exist in sheep. 2. Bronchial arterial blood flow to lower airways of both lungs of awake sheep was measured continuously using pulsed Doppler flow probes mounted on the bronchial artery at prior thoracotomy. 3. Cumulative and factorial analysis of responses to randomized combinations of autonomic alpha 1-, alpha 2-, beta 1- and beta 2-adrenoceptors and cholinoceptor autonomic blockade suggests that resting vasoconstrictor activity is less in sheep than in dogs. At normal aortic pressure, the autonomic activity of these receptor groups in the sheep lowers bronchial blood flow and conductance by 30%, whereas in the awake dog, the corresponding autonomic effect is 50%. 4. Tonic autonomic control of bronchial conductance can be partitioned in sheep to show significant and separate alpha- and beta-adrenoceptor vasoconstrictor activity at a ratio of 1.8:1, an effect normally offset by a weaker vasodilator alpha-/beta-adrenoceptor interaction. In contrast to the situation in awake dogs, cholinoceptors do not play a role in awake sheep. 5. Nitric oxide (NO) synthase inhibition in sheep using NG-nitro-L-arginine following blockade of alpha- and beta-adrenoceptors and cholinoceptors causes hypertension, but minor changes, if any, in pulmonary pressures or heart rate. Bronchial flow and conductance, however, fall from a higher resting conductance by approximately 50%, suggesting that, normally, resting bronchial flow conductance is dominated by strong tonic NO vasodilator effects that interact with weaker tonic autonomic vasoconstrictor effects. 6. Superimposed (respiratory) behaviours of sighing, sneezing and coughing, which involve negative swings in intrathoracic pressure and the movement of inspired air, evoke large active bronchovascular dilator effects. These appear to be largely NANC in origin and appear to be dependent, in part, on mechanisms associated with NO release. It is postulated that the C-fibre axon reflex using substance P, calcitonin gene-related peptide and neurokinin A may be involved. Vocalization and eructation do not evoke bronchovascular effects.
 ...
PMID:Autonomic control of bronchial circulation in awake sheep during rest and behaviour. 940 60


1 2 3 Next >>