Evidence For A Functional Contribution of Adenosine Signalling in Inflammatory Airway Diseases

Adenosine is a purine nucleoside of endogenous origin involved in a plethora of biological processes including neurotransmission, muscle contraction, cardiac function, haemostasis, vasodilatation, signal transduction, immune regulation, and inflammation/remodelling through specific stimulation of adenosine receptors. To date four subtypes of adenosine receptors have been identified; these are known as A1, A2A, A2B and A3 adenosine receptors. These are expressed on the cell membrane of a large variety of cell types, including inflammatory and structural cells, but their pattern of distribution, their specific function and affinity can vary in different cell types depending on the tissue milieu. This feature makes the understanding of adenosine regulated mechanisms in the pathogenesis of human diseases extremely challenging. Nonetheless, adenosine and its receptors are known to be pivotal in a wide range of disorders through modulation of specific biological responses in their respective organ systems. Adenosine and its receptors have been recently proposed to play a pro-inflammatory and immunomodulatory role in relation to the initiation and progression of several inflammatory disorders of the airways including asthma and chronic obstructive pulmonary disease (COPD). The objective of this article is to review the role of adenosine-receptor signaling in the respiratory system with special focus on chronic inflammatory airway diseases, such as asthma and COPD.