A3 adenosine receptor in the pulmonary system

Yifat Klein, Idit Matot*

*Corresponding author for this work

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

Abstract

A3 adenosine receptor (A3AR) is highly expressed in the airways of both man and other species. Within the human lungs, A 3AR appears mostly on circulating and resident inflammatory cells, particularly granular leukocytes such as eosinophils, neutrophils and monocytes. The human A3AR mediates anti-inflammatory cell responses upon its activation on these cells, via direct effect on cell migration, degranulation or the production of cytokines, however, stimulatory effects were also reported. In other species, high levels of A3AR expression were also found on lung mast cells. The A3AR has emerged as an AR subtype that may serve important regulatory roles in the inflamed airways. A3AR transcript and protein levels are elevated in lung biopsies from patients with asthma and chronic obstructive pulmonary disease, suggesting increased signaling through this receptor. The importance of eosinophils in allergy and asthma is well recognized. Therefore, current investigations evaluate the beneficial effect of targeting A3AR for the treatment of eosinophil-dependent pulmonary diseases such as asthma, chronic obstructive pulmonary disease and rhinitis. A3AR agonists also attenuate ischemia-reperfusion-induced lung injury in animal models, through the reduction of apoptosis, promotion of cell survival and anti-inflammatory effects. This protectivity is associated with a modified lobar arterial pressure which either evolves from the attenuated inflammation or results from a direct vascular impact of A3AR agonists. The role of A3AR in the pulmonary circulation remains to be elucidated. A3AR agonists were shown to exert species-dependent hemodynamic effects in the pulmonary system, mostly vasodilation. Still, thus far there is no data to demonstrate a direct effect of A3AR activation on the pulmonary vasculature, although an indirect effect was exhibited in rodents, through mast cell activation. This chapter summarizes current experimental and human data on the roles of A3AR in the healthy, injured and hyperresponsive airways and lungs and suggests that A 3AR may become a promising target to exploit in the development of innovative therapeutic strategies.

Original languageEnglish
Title of host publicationA3 Adenosine Receptors from Cell Biology to Pharmacology and Therapeutics
PublisherSpringer Netherlands
Pages209-233
Number of pages25
ISBN (Print)9789048131433
DOIs
StatePublished - 2010
Externally publishedYes

Keywords

  • A adenosine receptor
  • asthma
  • eosinophil
  • inflammation
  • lung injury

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