Extracellular adenosine 5′-triphosphate in pulmonary disorders

Adenosine 5′-triphosphate (ATP) is found in every cell of the human body where it plays a critical role in cellular energetics and metabolism. ATP is released from cells under physiologic and pathophysiologic condition; extracellular ATP is rapidly degraded to adenosine 5′-diphosphate (ADP) and adenosine by ecto-enzymes (mainly, CD39 and CD73). Before its degradation, ATP acts as an autocrine and paracrine agent exerting its effects on targeted cells by activating cell surface receptors named P2 Purinergic receptors. The latter are expressed by different cell types in the lungs, the activation of which is involved in multiple pulmonary disorders. This succinct review summarizes the role of ATP in inflammation processes associated with these disorders including bronchoconstriction, cough, mechanical ventilation-induced lung injury and idiopathic pulmonary fibrosis. All of these disorders still constitute unmet clinical needs. Therefore, the various ATP-signaling pathways in pulmonary inflammation constitute attractive targets for novel drug-candidates that would improve the management of patients with multiple pulmonary diseases.