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)

In guinea-pigs citric acid-induced cough and bronchoconstriction were inhibited by beta 2-agonist and xanthine drugs. Lidocaine inhibited only cough. Cromoglycate and ipratropium bromide inhibited only bronchoconstriction. We conclude that cough and bronchoconstriction in guinea-pigs are distinct reflexes and that the inhibitory pharmacology of these airway reflexes may agree in many respects, with that observed in asthmatic subjects.
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PMID:Selective inhibition of cough and bronchoconstriction in conscious guinea pigs. 153 22

The effects of nebulized diuretics on citric acid-induced cough and airway obstruction in guinea pigs and capsaicin-induced cough and increase in airway resistance in humans have been studied. Half-maximum inhibition of cough in the guinea pig was produced by 1.3 mM furosemide and 0.25 mM hydrochlorothiazide. Cough was inhibited by 78 +/- 9% by 3 mM furosemide (P less than 0.05) and 89 +/- 11% by 3 mM hydrochlorothiazide (P less than 0.01). At the same time, airway obstruction was inhibited by 50 +/- 9% (P less than 0.001) and 42 +/- 15% (P less than 0.05), respectively. Nebulized furosemide (3 mM) was without effect on the airway obstruction produced by inhaled histamine or acetylcholine in the guinea pigs. Intravenously administered furosemide (270 nmol/kg) did not affect citric acid-induced responses. In humans, aerosolized furosemide (9 mM) and hydrochlorothiazide (3.4 mM) reduced the percent increase in respiratory resistance from 22.1 +/- 3.7 and 15.6 +/- 3.4 to 10.5 +/- 4.9 and 9.4 +/- 3.3%, respectively (P less than 0.05), but were without effect on cough due to capsaicin. Thus both furosemide and hydrochlorothiazide inhibited airway obstruction in the guinea pig and reduced the capsaicin-induced increase in airway resistance in humans. However, whereas coughing was inhibited in the guinea pig, neither drug affected cough in humans. This difference in the action of the loop diuretic and thiazide, which interact differently with Na(+)-K(+)-Cl-transport within the airway mucosa, on the cough and airflow obstruction in guinea pig and humans supports the view that different sensory limbs are involved in these reflexes.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:A comparison of the effect of inhaled diuretics on airway reflexes in humans and guinea pigs. 155 16

1. Twelve non-smoking subjects inhaled capsaicin at three different inspiratory flow rates: 50, 100 and 150 litres/min. Capsaicin was delivered by a breath-actuated dosimeter; inhalations consisted of 0.21-13.6 nmol of capsaicin in doubling amounts given in random order. 2. The mean number of coughs per challenge decreased with increasing inspiratory flow rate. The difference in cough numbers were significant: 7.7 (95% confidence interval 2.5-12.8) for 50 versus 100 litres/min and 10.9 (95% confidence interval 5.0-16.9) for 100 versus 150 litres/min. 3. On a separate day, a cough threshold was measured by giving increasing doses of citric acid that were inhaled at 50 litres/min. There was a positive correlation between the sensitivity to capsaicin and the cough threshold to citric acid (r = 0.69, P = 0.01), and also between the cough latencies (r = 0.67, P = 0.02). 4. The negative relationship between the cough response and the inspiratory flow rate may be caused by increased laryngeal deposition at lower inspiratory flow rates. 5. These results are compatible with a similar anatomical distribution of cough receptors for capsaicin and citric acid. 6. These results suggest that changes in inspiratory flow rate may affect the results of cough challenges.
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PMID:Effect of changes in inspiratory flow rate on cough responses to inhaled capsaicin. 165 2

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.
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PMID:Selectivity of ruthenium red in inhibiting bronchoconstriction and CGRP release induced by afferent C-fibre activation in the guinea-pig lung. 171 14

The influence of aerosols of Ruthenium red (RR) on capsaicin- and citric acid-induced cough was investigated in guinea pigs. Aerosols of RR (0.3, 1, 3%) reduced capsaicin-induced cough in dose-dependent manner. Inhalation of RR also reduced cough produced by low, (200 mM) but not high (550 mM), concentrations of citric acid. These data suggest that RR is not a specific capsaicin antagonist and that citric acid and capsaicin share a common mechanism for activation of airway C-fibers that is RR sensitive. Furthermore, high concentrations of citric acid can elicit cough through a RR-insensitive mechanism.
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PMID:Ruthenium red decreases capsaicin and citric acid-induced cough in guinea pigs. 171 93

We studied the effects of angiotensin converting enzyme (ACE) inhibitors on cough responses to bradykinin (BK), substance P (SP) and citric acid in a double blind, random study on 10 hypertensive patients receiving ACE inhibitors. Of these patients, five had reported cough with ACE inhibitors. Cough responses to citric acid were similar between patients with and without cough, and SP up to 10(-5) M did not cause cough in any of the subjects. BK caused cough at 13.4 +/- 1.2 (-log M) in 5 patients with cough associated with ACE inhibitors, but it did not cause cough at concentrations up to 10(-5) M in other 5 patients. One month after the withdrawal of ACE inhibitors, 5 patients were free from cough symptoms, and BK did not cause cough up to 10(-5) M in these patients, except for one who coughed at 10(-9) M, without changes in responses to citric acid. BK caused cough at 14.3 +/- 0.7 (-log M) although BK1-7, a major metabolite of BK by ACE, caused cough at 5.7 +/- 0.7 (-log M) in another 3 patients with cough associated with ACE inhibitor. These results suggest that impaired metabolism of BK induced by ACE inhibitors may relate to the manifestation of cough in hypertensive patients receiving ACE inhibitors.
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PMID:Bradykinin-induced cough reflex markedly increases in patients with cough associated with captopril and enalapril. 172 Dec 46

1. Comparisons were made between the doses required of aerosol and intraperitoneally administered morphine, dextromethorphan, codeine and the specific peripherally acting mu-receptor agonist DALDA (H-Tyr-D-Arg-Phe-Lys-NH2) to suppress citric acid-induced coughing in conscious guinea pigs. 2. Estimated ID50s for inhibition of numbers of coughs induced by an aerosol of 5% citric acid were 1.0 and 2.4 mg/kg for intraperitoneally administered morphine and dextromethorphan, respectively. 3. The estimated ID50s after inhalation of morphine and dextromethorphan as aerosols were approximately 2.2 and approximately 12 micrograms/kg, respectively. 4. Aerosilized codeine (approximately 72 micrograms/kg, n = 5) significantly inhibited coughing by 62 +/- 23% whereas 3 mg/kg, i.p. was required to significantly reduce coughing by a similar degree (60 +/- 6%, n = 7). 5. Inhalation of DALDA (approximately 7.2 micrograms/kg, n = 7) also significantly inhibited coughing. 6. The antitussive effect of inhaled morphine (approximately 7.2 micrograms/kg, n = 11) was inhibited after administration of 3 mg/kg of either naloxone hydrochloride or naloxone methylbromide intraperitoneally. 7. The results support the hypothesis that effects at a peripheral site can make a major contribution to the antitussive actions of these drugs.
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PMID:Evidence for peripheral mechanisms mediating the antitussive actions of opioids in the guinea pig. 181 Aug 7

This controlled crossover study in twenty healthy volunteer subjects utilized the citric acid aerosol-induced cough response as a means to demonstrate the effectiveness of 25 mg of diphenhydramine as an antitussive. Entry was limited to only those subjects who manifested a consistent, quantitatively definable response to a 5% citric acid challenge. Subjects were initially dosed with either a placebo vehicle or 25 mg diphenhydramine in a 10 ml formulation. Following drug ingestion, subjects were challenged at 15, 30, 45, 60, 120, and 240 minutes. Three days later, subjects were administered the alternate treatment and rechallenged at the same time points. Diphenhydramine was effective at the earliest time point assessed, 15 minutes, and continued to be as effective over the entire 4-hour duration of the test period. For the placebo vehicle, the mean cough counts did not change significantly from baseline. Neither the putative soothing effect of a liquid formulation nor accommodation to the citric acid spray can account for all the early and consistently significant activity of diphenhydramine in suppressing the cough response. The early onset of activity of diphenhydramine may be due to its local anesthetic properties or may indicate that the dose of diphenhydramine required for effective antitussive activity is lower than that required for effective antihistaminic activity. These results require further corroboration in direct comparisons of various doses of diphenhydramine with positive controls in both this model and clinical cough counting models employing pathologic cough indices. A 25 mg dose of diphenhydramine appears to be effective as an antitussive agent.
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PMID:Antitussive effects of diphenhydramine on the citric acid aerosol-induced cough response in humans. 186 43

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.
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PMID:Hyperresponsiveness to tussive stimuli in cigarette smoke-exposed guinea-pigs: a role for capsaicin-sensitive, calcitonin gene-related peptide-containing nerves. 187 46

The effect of 50 min cigarette smoke exposure on airway responsiveness to the bronchoconstrictor and tussive effects of histamine and citric acid has been examined in guinea-pigs. Intravenous histamine increased intratracheal pressure (ITP) in anaesthetized guinea-pigs and the dose-response curve was significantly (P less than 0.05) steeper in cigarette smoke- than in air-exposed animals. ED50 values were 11.4 nmol kg-1 (7.4-16.8, 95% confidence interval) and 42.5 nmol kg-1 (28.8-61.4, 95% confidence interval), respectively (P less than 0.05) in smoke- and air-exposed guinea-pigs indicating an enhanced reactivity. However, the sensitivity to intravenous histamine was not changed by the cigarette smoke exposure, and the maximum increase in intratracheal pressure was the same as in control animals (air: 247 +/- 21%, n = 4; smoke: 223 +/- 18%, n = 7). The cigarette smoke-induced hyperresponsiveness to intravenous histamine was not altered by pretreatment with nebulized lidocaine (0.20 M), ipratropium bromide (0.30 mM) or cromoglycate (0.06 M), suggesting that a neural reflex is unlikely to be involved in the development of hyperresponsiveness. Conscious, smoke-exposed guinea-pigs had a significantly (P less than 0.001) reduced responsiveness to citric acid (0.40 M) and cigarette smoke. Both cough and bronchoconstriction were suppressed for about 1 h, but unchanged 24 h after exposure. The hyporesponsiveness to citric acid was inhibited by atropine (1.4 mumol kg-1 i.p.) and may therefore, at least in part, be due to increased airway secretions. The present data demonstrate that inhalation of cigarette smoke may alter guinea-pig airway responsiveness to tussive and bronchoconstrictor stimuli.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cigarette smoke-induced changes in guinea-pig airway responsiveness to histamine and citric acid. 187 60


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