Journal of Pharmacovigilance

ATP axis in chronic obstructive pulmonary diseases: Opportunities for novel drugs development

Conference Series LLC Joint International Event on 7^th Pharmacovigilance & Pharmaceutical Industry

August 22-24, 2016 Vienna, Austria

Amir Pelleg

Danmir Technologies, USA
Drexel University School of Medicine, USA

Posters & Accepted Abstracts: J Pharmacovigil

Abstract:

In 2002 we have proposed for the first time that extracellular adenosine 5�??-triphosphate (ATP) plays an important mechanistic role in chronic obstructive pulmonary diseases. This hypothesis was based on the well documented release of ATP from cells under pathophysiologic conditions and our original studies, in which we have demonstrated that ATP causes bronchoconstriction and facilitates cough as well as enhancement of the immune reaction-dependent histamine-release from human lung mast cells, and increased levels of free [Ca2+]i in human eosinophils. These actions of ATP are mediated by direct activation of specific P2 receptors (P2R) subtypes and are independent of adenosine, the product of ATP�??s degradation by ecto-enzymes. Subsequent studies by us and others in animal models and human subjects have generated voluminous data supporting our original hypothesis. For example, we have shown that aerosolized ATP is a potent bronchoconstrictor in asthmatic and COPD patients and that this action is not mediated by adenosine. In addition, the level of ATP in the lungs of COPD patients is x3 that found in normal subjects. Others have documented a mechanistic role of ATP in pulmonary inflammation, which is mediated by P2R as well as a facilitating role of ATP as a tussigenic agent. Taken together, these results constitute a strong rationale for the development of novel drug candidates for the treatment of COPD, asthma and chronic cough. The current state-of-the-art in this arena will be presented and new opportunities will be outlined.

Biography :

Email: Amir.Pelleg@DrexelMed.edu