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Pharmacological modulation of adenosine system: Novel options for treatment of inflammatory bowel diseases

Antonioli, Luca PhD1; Fornai, Matteo PhD1; Colucci, Rocchina PhD1; Ghisu, Narcisa PharmD1; Tuccori, Marco PharmD1; Del Tacca, Mario MD1; Blandizzi, Corrado MD1,*

doi: 10.1002/ibd.20316
Basic Science Review

Inflammatory bowel diseases (IBDs) are chronic disorders resulting from abnormal and persistent immune responses which lead to severe tissue injury and disturbances in digestive motor/secretory functions. At present, pharmacotherapy represents the cornerstone for the management of IBDs, and recent advances in understanding the immunopathogenesis of intestinal inflammation suggest the adenosine system as an attractive target for development of novel drugs against gut inflammatory disorders. Consistent evidence indicates that adenosine plays a relevant role in the regulation of immune system via interaction with specific cell‐membrane G‐protein‐coupled receptors (A1, A2a, A2b, and A3). Moreover, this nucleoside is implicated in the control of enteric neurotransmission and gut motor functions. In the presence of inflammation, the adenosine system acts as a sensible sensor apparatus, which, through dynamic modifications in the expression of ecto‐enzymes and purinergic receptors, adapts its metabolism to tissue health status and contributes to the mechanisms deputed to the protection of tissues against inflammatory injuries. In keeping with these concepts, it is becoming increasingly appreciated that drugs targeted on adenosine receptors or enzymes responsible for adenosine catabolism can exert beneficial effects on experimental models of intestinal inflammation. This review aims to discuss the role of adenosine in the regulation of enteric immune responses and gut neuromuscular functions in the presence of inflammation, as well as to highlight the mechanisms through which the pharmacological modulation of adenosine pathways may have potential applications for the therapeutic management of IBDs.

1Division of Pharmacology and Chemotherapy, Department of Internal Medicine, University of Pisa, Pisa, Italy

* Divisione di Farmacologia e Chemioterapia, Dipartimento di Medicina Interna, Università di Pisa, Via Roma 55, 56126 – Pisa, Italy (e‐mail: c.blandizzi@virgilio.it)

Received 29 August 2007; Accepted 19 September 2007

Published online 16 November 2007 in Wiley InterScience (www.interscience.wiley.com).

© Crohn's & Colitis Foundation of America, Inc.
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