Effect of bumetanide on toluene diisocyanate induced contractions in guinea pig airways.

Mapp, C. E.; Boniotti, Anna; Papi, Alberto; Maggi, C.A.; Stefano, Antonino Di; Saetta, Marina; Ciaccia, A.; Fabbri, Leonardo

doi:10.1136/thx.48.1.63

Cited by 12 publications

(13 citation statements)

References 23 publications

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“…On the other hand, these results may also suggest that these nerves do not necessarily display the same prejunctional modulatory receptors. Recently, it has been demonstrated that loop diuretics (frusemide and bumetanide) are able to inhibit the cholinergic, as well as the noncholinergic contraction [26,27], and the nonadrenergic relaxation in guinea-pig airways in vitro [17]. These results are not in contradiction with the present results, since loop diuretics do not act through stimulation of a prejunctional receptor but probably through inhibition of nerve activation (myelinated cholinergic nerves as well as unmyelinated C-fibres)…”

Section: Discussioncontrasting

confidence: 57%

Opioids modulate the cholinergic contraction but not the nonadrenergic relaxation in guinea-pig airways in vitro

Pype¹,

Dupont²,

Demedts³

et al. 1996

Eur Respir J

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O Op pi io oi id ds s m mo od du ul la at te e t th he e c ch ho ol li in ne er rg gi ic c c co on nt tr ra ac ct ti io on n b bu ut t n no ot t t th he e n no on na a--d dr re en ne er rg gi ic c r re el la ax xa at ti io on n i in n g gu ui in ne ea a--p pi ig g a ai ir rw wa ay ys s i in n v vi it tr ro o DAMGO (1-100 µM) inhibited the cholinergic contraction in the upper trachea with a maximum inhibition of 57±15% at 1 Hz (n=4; p<0.05). On the other hand, DPDPE (10 µM) and U69593 (10 µM) did not produce any significant inhibition of the cholinergic contraction. Naloxone, an opioid receptor antagonist (100 µM), was able to antagonize the inhibitory effect of DAMGO (n=5; p<0.01) on the cholinergic contraction at a frequency of 2 Hz. DAMGO (10 µM) did not displace the cumulative concentration-response relationship to acetylcholine (10 nM-10 mM), (n=4; NS). This provides evidence that prejunctional µ-opioid receptors (and not δ-opioid or κ-opioid receptors) modulate cholinergic contraction in the upper trachea. In contrast, DAMGO (10 µM) had no significant inhibitory effect on the nonadrenergic relaxation (n=4; NS) in the upper trachea. Neither DPDPE nor U-69593 had any effect on the nonadrenergic relaxation.These findings suggest that DAMGO directly inhibits the cholinergic contraction and that the opioid receptor involved in the inhibition of the cholinergic contraction in the upper trachea is of the µ-opioid type. The finding that opioids inhibit cholinergic contraction without altering NANC relaxations suggests that distinct populations of nerves mediate these two effects.

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Section: Discussioncontrasting

confidence: 57%

Opioids modulate the cholinergic contraction but not the nonadrenergic relaxation in guinea-pig airways in vitro

Pype¹,

Dupont²,

Demedts³

et al. 1996

Eur Respir J

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“…One of the consequences of this inflammation is airway epithelial damage [23]. In fact, several in vitro studies have shown that epithelial damage leads to increased bronchial responsiveness to different pharmacological agonists [11,24,25]. Serosal versus mucosal application of agonist ligands also leads to increased bronchial responsiveness [26], but the denudation of epithelium abolished this increased responsiveness [27].…”

Section: Discussionmentioning

confidence: 99%

“…Thus, airway inflammation can cause epithelial damage; and this, in turn, can result in a better access of ligands to the active sites in the airways, causing bronchial hyperresponsiveness in asthma. Damage of the epithelial layer of the tracheobronchial tree in asthma could lead to airway hyperresponsiveness by several other mechanisms including: exposure of sensory nerve fibres and activation of local reflex mechanisms [31], changes in osmolarity of the airway surface lining fluid [32], loss of neutral endopeptidase [25] which degrades tachykinins such as substance P, reduction of epithelial-derived relaxant factor [33] and release of spasmogen mediators such as endothelin [34]. However, these factors cannot affect antagonist blockade and some of these factors are unlikely to affect airway responsiveness to methacholine in vitro in our preparation.…”

Section: Discussionmentioning

confidence: 99%

Increased Muscarinic Receptor Blockade by Atropine in Tracheal Chains of Ovalbumin-Sensitized Guinea Pigs

Boskabady

Adel-Kardan

1999

Pharmacology

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Drug delivery to the receptor sites and receptor affinity could be determinant factors for increased bronchial responsiveness seen in asthma. Competitive antagonism blockade which is measured as dose ratio – 1 (DR-1) depends only on these two factors. Therefore, in this study we examined the muscarinic receptor blockade by atropine on isolated tracheal chains of sensitized compared to control guinea pigs. An experimental model of asthma was induced in guinea pigs by sensitization of animals with injection and inhalation of ovalbumin (OA). The responses of tracheal chains of sensitized and control animals (for each group n = 10) to cumulative concentrations of methacholine in the absence and presence of 5 nmol/l atropine were measured, and the effective concentrations of methacholine causing 50% of maximum response (EC₅₀ M) were obtained. The atropine blockade (DR-1) was calculated by: (post-atropine EC₅₀ M/EC₅₀ M) – 1. The responses of tracheal chains to 0.1% OA, relative to contraction obtained by 10 mmol/l methacholine, were also measured. The tracheal responses of sensitized guinea pigs were significantly higher than those of control animals to both OA (mean ± SEM, 55.94 ± 5.22 vs. 2.59 ± 0.85%, p < 0.001) and methacholine (EC₅₀ M for asthmatic and control animals were 0.88 ± 0.27 and 2.00 ± 0.26 μmol, respectively, p < 0.01). The muscarinic receptor blockade by atropine (DR-1) was also significantly higher in tracheas of asthmatic compared to that of control animals (131.12 ± 19.82 vs. 24.50 ± 3.19, p < 0.001). There were significant correlations between tracheal response to OA and EC₅₀ M (r = –0.644, p = 0.002) and also between DR-1 and tracheal responses to both OA (r = 0.738, p < 0.001) and EC₅₀ M (r = –0.679, p < 0.001). This enhanced muscarinic receptor blockade in tracheal chains of sensitized animals confirms our previous findings which was predicted to be due to the increased drug delivery to the receptors. Drug delivery could also be a determinant factor for bronchial responsiveness to stimuli in asthma.

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“…It also inhibits neutral endopeptidase in experimental animals and in vitro preparations [110,111]. The activation of sensory nerves is likely to be indirect, through the release of prostanoids [112,113].…”

Section: Neurogenic Inflammationmentioning

confidence: 99%

Mechanisms and pathology of occupational asthma

Mapp

Saetta²,

Maestrelli³

et al. 1994

Eur Respir J

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M Me ec ch ha an ni is sm ms s a an nd d p pa at th ho ol lo og gy y o of f o oc cc cu up pa at ti io on na al l a as st th hm ma a More than one mechanism may be operative in occupational asthma. Among the mechanisms proposed, immunological mechanisms and airway inflammation play an important role. There is evidence to confirm that T-lymphocyte activation and local accumulation in the bronchial wall of activated eosinophils occurs in asthma of diverse aetiology, i.e. immunoglobulin E (IgE)-mediated, occupational and intrinsic.Neurogenic pathways should be further investigated as a potential mechanism of modulation and amplification of airway inflammation in occupational asthma.

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Effect of bumetanide on toluene diisocyanate induced contractions in guinea pig airways.

Abstract: Background The loop diuretic frusemide has been shown to inhibit the bronchoconstrictor response to exercise, inhaled allergen, distilled water, adenosine, and sodium metabisulphite. Toluene diisocyanate contracts smooth

Cited by 12 publications

References 23 publications

Opioids modulate the cholinergic contraction but not the nonadrenergic relaxation in guinea-pig airways in vitro

Opioids modulate the cholinergic contraction but not the nonadrenergic relaxation in guinea-pig airways in vitro

Increased Muscarinic Receptor Blockade by Atropine in Tracheal Chains of Ovalbumin-Sensitized Guinea Pigs

Mechanisms and pathology of occupational asthma

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