Beta-adrenergic agonists and bronchial hyperreactivity: role of beta2-adrenergic and tachykinin neurokinin-2 receptors.

Abstract

BACKGROUND:

beta(2)-Adrenergic agonists are the most widely used bronchodilators for the treatment of asthma. On the other hand, there is concern that excessive use of beta(2)-agonists may contribute to the exacerbation of asthma. However, the mechanism of such adverse effects of beta(2)-agonists is not completely clear.

OBJECTIVE:

The aim of this study was to assess the direct influence of beta(2)-agonists on airways by analyzing the effect of a beta(2)-agonist, fenoterol, on airway sensitivity in an animal model and on tachykinin neurokinin-2 receptor expression in bovine tracheal smooth muscle.

METHODS:

We performed an acetylcholine challenge test on ovalbumin sensitized guinea pigs that were exposed to daily inhalation of ovalbumin and fenoterol. We also investigated the effects of fenoterol on neurokinin-2 receptor messenger RNA and density with Northern blot analysis and receptor binding assay.

RESULT:

The increase of airway responsiveness and the decrease of beta(2)-adrenergic receptors were found in guinea pigs that were treated with fenoterol. There were time- and dose-dependent increases of neurokinin-2 receptor mRNA and of density in tracheal smooth muscle that was treated with fenoterol.

CONCLUSION:

This increased airway responsiveness, increased neurokinin-2 receptor expression, and decreased beta(2)-adrenergic receptor density may be relevant to asthma exacerbation.

• Authors: T Katsunuma, K Fujita, J C Mak, P J Barnes, K Ueno, Y Iikura
• Journal: The Journal of allergy and clinical immunology (J Allergy Clin Immunol) Vol. 106 Issue 1 Pt 2 Pg. S104-8 (Jul 2000) ISSN: 0091-6749 [Print] United States
• PMID: 10887342 (Publication Type: Journal Article)

Chemical References

• Adrenergic beta-Agonists
• Receptors, Adrenergic, beta-2
• Receptors, Neurokinin-2
• Fenoterol

Topics

• Adrenergic beta-Agonists (adverse effects, pharmacology)
• Animals
• Asthma (mortality)
• Bronchial Hyperreactivity (chemically induced, physiopathology)
• Cattle
• Fenoterol (adverse effects, pharmacology)
• Guinea Pigs
• Male
• Muscle, Smooth (drug effects)
• Receptors, Adrenergic, beta-2 (physiology)
• Receptors, Neurokinin-2 (physiology)
• Trachea (drug effects)