Targeting the ATP-Axis in Lungs as a New Therapheutic Modality for COPD

Adenosine 5’-triphosphate (ATP) is found in every cell of the body where it plays a critical role in cellular metabolism and energetics. ATP is released from cells under physiologic and pathophysiologic conditions; extracellular ATP acts as an autocrine and paracrine agent. Its effects on targeted cells are mediated by subtypes of purinergic receptors (P2R). In the lungs, relatively large amounts of ATP are released under inflammatory conditions. Extracellular ATP triggers a central vagal reflex by activating purinergic receptor P2XR localized on pulmonary vagal sensory nerve terminals. This results in cough, bronchoconstriction and the release of pro-inflammatory neuropeptides via axon reflex. COPD patients manifest higher sensetivity to aerosolized ATP than healthy subjects, and the levels of ATP in COPD patients’ lungs are 3x that found in healthy subjects. This review succinctly details (i) the sources amd mechanisms of ATP’s release into the extracellular space, (ii) the ways extracellular ATP is eliminated, (iii) the deleterious effects of ATP in the lungs in general and in COPD in particular, and (iv) the rationale for the blockade of these actions of ATP in the lungs as a novel therapeutic approach in the management of COPD patients.