Dictionary of Allergies .. Adenosine receptors

Adenosine receptors

Adenosine is a natural nucleotide that plays a physiological role in the modulation of human inflammatory cells and regulates tissue function by activating four G-protein-coupled adenosine receptors: A1, A2A, A2B and A3 [1]. Human B and T (OKT4+and OKT8+) lymphocytes, polymorphonuclear leucocytes, monocytes, basophils and platelets possess a membrane adenosine α2/β2 receptor. Several studies led to the identification of R receptor site, with which adenosine interacts to produce its physiologic effects on a variety of organ systems, including the heart, gut and nervous system. The ability of the adenosine-uptake inhibitor dipyridamol, to potentiate these actions of the nucleoside indicated that they might be mediated by stimulation of cell-surface receptors. R receptors subtypes are now recognized: interaction of the nucleoside with the Ra(A2) receptors stimulates adenylate-cyclase activity, while its interaction with the Ri(A1) receptor causes inhibition. The receptor subtypes are recognized by the relative potency with which various adenosine analogs interact with them [2].

Animal models of asthma, ischaemia, arthritis, sepsis, inflammatory bowel disease and wound healing have helped to elucidate the regulatory roles of the various adenosine receptors in dictating the development and progression of disease. This recent heightened awareness of the role of adenosine in the control of immune and inflammatory systems has generated excitement regarding the potential use of adenosine-receptor-based therapies in the treatment of infection, autoimmunity, ischaemia and degenerative diseases[1].

A growing body of evidence has emerged in support of a pro-inflammatory role for adenosine in the pathogenic mechanisms of chronic inflammatory disorders of the airways such as asthma and COPD. The demonstration that adenosine enhances mast cell allergen-dependent activation, the notion that elevated levels of adenosine are present in chronically inflamed airways, and the results from exposure studies of nebulised adenosine showing dose-dependent bronchoconstriction in subjects with asthma and COPD, emphasise the importance of adenosine in the initiation, persistence and progression in these common inflammatory disorders of the airways. Adenosine exerts its manifold biological activities by interacting with at least four adenosine receptor subtypes. Selective activation or blockade of these sites is being exploited by the pharmaceutical industry in an attempt to generate novel therapies for asthma and COPD[3].

References

1. Haskó G, Linden J, Cronstein B, Pacher P. Adenosine receptors: therapeutic aspects for inflammatory and immune diseases. Nat Rev Drug Discov. 2008 Sep;7(9):759-70.
 

2 . Marone G, Petracca R, Vigorita S. Adenosine receptors on human inflammatory cells. . Int Arch Allergy Appl Immunol. 1985;77(1-2):259-63.

Allergy Appl. Immunol. 77. No. 1-2, p. 259, 1985.
3. Polosa R, Holgate ST. Adenosine receptors as promising therapeutic targets for drug development in chronic airway inflammation. Curr Drug Targets. 2006 Jun;7(6):699-706.