Why do asthmatic subjects respond so strongly to inhaled adenosine?

Bronchospasm induced by adenosine is blocked by representatives of all the major classes of drugs used in the treatment of asthma. Understanding the mechanism of this bronchospasm may help understand the way these drugs work. Clinical studies have suggested involvement of neural pathways, mast-like...

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Veröffentlicht in:Life sciences (1973) 2001-08, Vol.69 (11), p.1225-1240
Hauptverfasser: Meade, Christopher J., Dumont, Indepencia, Worrall, Liam
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container_end_page 1240
container_issue 11
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container_title Life sciences (1973)
container_volume 69
creator Meade, Christopher J.
Dumont, Indepencia
Worrall, Liam
description Bronchospasm induced by adenosine is blocked by representatives of all the major classes of drugs used in the treatment of asthma. Understanding the mechanism of this bronchospasm may help understand the way these drugs work. Clinical studies have suggested involvement of neural pathways, mast-like cells and mediators such as histamine, serotonin and lipoxygenase products. There is a strong link between responsiveness to adenosine and eosinophilia. In different animal models A 1, A 2b and A 3 adenosine receptor subclasses have all been implicated in inducing bronchospasm, whilst occupation of the A 2a receptor generally has no, or the opposite effect. At least two different mechanisms, both involving neural pathways, exist. One, involving the adenosine A 1 receptor, functions in mast cell depleted animals; the other requires interaction with a population of mast-like cells activated over A 2b or A 3 receptors. Not only histamine but also serotonin and lipoxygenase products released from the mast-like cells are potential mediators. In animal models good reactivity to adenosine receptor agonists is generally only found when the animals are first sensitized and exposed to allergen in ways likely to induce an allergic inflammation. An exception is the BDE rat, which reacts to adenosine receptor agonists such as APNEA or NECA even without allergen exposure. This rat strain does however show evidence of spontaneous eosinophilic inflammation in the lung even without immunization. As mast cells both release adenosine and respond to adenosine, adenosine provides a non-specific method of amplifying specific signals resulting from IgE / antigen interaction. This mechanism may not only have a pathological significance in asthma; it may be part of a normal bodily defense response that in asthmatic subjects is inappropriately activated.
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source MEDLINE; ScienceDirect Journals (5 years ago - present)
subjects Adenosine
Adenosine-5'-(N-ethylcarboxamide) - administration & dosage
Administration, Inhalation
Animals
Asthma
Asthma - physiopathology
Bronchial Spasm - physiopathology
Bronchoconstriction - drug effects
Bronchoconstriction - physiology
Disease Models, Animal
Eosinophil
Eosinophilia - physiopathology
Humans
Hyperreactivity
In Vitro Techniques
Mast Cells - physiology
Rats
Rats, Inbred Strains
Receptors, Purinergic P1 - classification
Receptors, Purinergic P1 - physiology
Vasodilator Agents - administration & dosage
title Why do asthmatic subjects respond so strongly to inhaled adenosine?
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