Adenosine receptors and asthma.
The pathophysiological processes underlying respiratory diseases like asthma are complex, resulting in an overwhelming choice of potential targets for the novel treatment of this disease. Despite this complexity, asthmatic subjects are uniquely sensitive to a range of substances like adenosine, thought to act indirectly to evoke changes in respiratory mechanics and in the underlying pathology, and thereby to offer novel insights into the pathophysiology of this disease. Adenosine is of particular interest because this substance is produced endogenously by many cells during hypoxia, stress, allergic stimulation, and exercise. Extracellular adenosine can be measured in significant concentrations within the airways; can be shown to activate adenosine receptor (AR) subtypes on lung resident cells and migrating inflammatory cells, thereby altering their function, and could therefore play a significant role in this disease. Many preclinical in vitro and in vivo studies have documented the roles of the various AR subtypes in regulating cell function and how they might have a beneficial impact in disease models. Agonists and antagonists of some of these receptor subtypes have been developed and have progressed to clinical studies in order to evaluate their potential as novel antiasthma drugs. In this chapter, we will highlight the roles of adenosine and AR subtypes in many of the characteristic features of asthma: airway obstruction, inflammation, bronchial hyperresponsiveness and remodeling. We will also discuss the merit of targeting each receptor subtype in the development of novel antiasthma drugs.
Wilson
Constance N
CN
Endacea, Inc., Research Triangle Park, NC 27709-2076, USA. cwilson@endacea.nctda.org
Nadeem
Ahmed
A
Spina
Domenico
D
Brown
Rachel
R
Page
Clive P
CP
Mustafa
S Jamal
SJ
D000241:Adenosine / Q000378:metabolism; D000818:Animals; D001249:Asthma / Q000209:etiology*; D016084:Bronchoconstriction / Q000502:physiology; D006801:Humans; D043682:Receptor, Adenosine A1 / Q000502:physiology; D043705:Receptor, Adenosine A2A / Q000502:physiology; D043704:Receptor, Adenosine A2B / Q000502:physiology; D043684:Receptor, Adenosine A3 / Q000502:physiology; D018047:Receptors, Purinergic P1 / Q000502:physiology*
D043682:Receptor, Adenosine A1; D043705:Receptor, Adenosine A2A; D043704:Receptor, Adenosine A2B; D043684:Receptor, Adenosine A3; D018047:Receptors, Purinergic P1; D000241:Adenosine