Contrasting effects of ATP and adenosine on capsaicin challenge in asthmatic patients

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Title: Contrasting effects of ATP and adenosine on capsaicin challenge in asthmatic patients
Authors: Basoglu, OK
Pelleg, A
Kharitonov, SA
Barnes, PJ
Item Type: Journal Article
Abstract: Background Adenosine 5’-triphosphate (ATP) stimulates pulmonary vagal slow conducting C-fibres and fast conducting Aδ-fibres with rapidly adapting receptors (RARs). Pulmonary C-fibres but not RARs are also sensitive to capsaicin, a potent tussigenic agent in humans. Thus, the aim of this study was to determine the effects of ATP and its metabolite adenosine (given as adenosine 5’-monophosphate, AMP) on capsaicin challenge in asthmatic patients. Methods Cough (quantified as visual analogue scale, VAS), dyspnoea (quantified as Borg score), and FEV1 were quantified following bronchoprovocation using capsaicin, adenosine and ATP in healthy non-smokers (age 40±4y, 6 males), smokers (45±4y, 5 males) and asthmatic patients (37±3y, 5 males); n = 10 in each group. Results None of the healthy non-smokers responded to either AMP or ATP. AMP induced bronchoconstriction in one smoker and eight asthmatics, and ATP in two smokers and all ten asthmatics. The geometric mean of capsaicin causing ≥5 coughs (C5) increased from 134 to 203 μM in non-smokers and from 117 to 287 μM in asthmatics after AMP, whereas it decreased from 203 to 165 μM and 125 to 88 μM, respectively after ATP. AMP decreased C5 from 58 to 29 μM and ATP increased from 33 to 47 μM in smokers. However, due to intergroup variability, these effects of ATP and AMP were not statistically significant (0.125 ≤ p ≤ 0.998). That notwithstanding, in healthy and asthmatic subjects the effects of the ATP showed a tendency to be greater than those of AMP (p < 0.053). Dyspnea, assessed by Borg score, increased after ATP (p < 0.001) and AMP (p < 0.001) only in asthmatic patients. Intensity of cough assessed by VAS increased (p < 0.05) after second capsaicin challenges performed after AMP in all groups, but not after ATP. Conclusions Asthmatic patients exhibit hypersensitivity to aerosolized AMP and ATP, but aerosolized AMP does not mimic the effects of ATP and the effects of ATP are not mediated by adenosine.
Issue Date: 6-Apr-2017
Date of Acceptance: 5-Apr-2017
URI: http://hdl.handle.net/10044/1/52034
DOI: https://dx.doi.org/10.1016/j.pupt.2017.04.004
ISSN: 1094-5539
Publisher: Elsevier
Start Page: 13
End Page: 18
Journal / Book Title: Pulmonary Pharmacology and Therapeutics
Volume: 45
Copyright Statement: © 2017, Elsevier. Licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International http://creativecommons.org/licenses/by-nc-nd/4.0/
Keywords: Science & Technology
Life Sciences & Biomedicine
Pharmacology & Pharmacy
Respiratory System
Asthma
Cough
Puirinergic receptors
Vagus
OBSTRUCTIVE PULMONARY-DISEASE
RECEPTOR SUBTYPES
NERVE-TERMINALS
COUGH REFLEX
5'-TRIPHOSPHATE
CELLS
COPD
LUNG
5'-MONOPHOSPHATE
NUCLEOTIDES
Asthma
Cough
Puirinergic receptors
Vagus
Science & Technology
Life Sciences & Biomedicine
Pharmacology & Pharmacy
Respiratory System
Asthma
Cough
Puirinergic receptors
Vagus
OBSTRUCTIVE PULMONARY-DISEASE
RECEPTOR SUBTYPES
NERVE-TERMINALS
COUGH REFLEX
5'-TRIPHOSPHATE
CELLS
COPD
LUNG
5'-MONOPHOSPHATE
NUCLEOTIDES
1103 Clinical Sciences
1115 Pharmacology And Pharmaceutical Sciences
Respiratory System
Publication Status: Published
Appears in Collections:National Heart and Lung Institute
Airway Disease
Faculty of Medicine



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