ATP in central respiratory control: A three-part signaling system

The landmark demonstrations in 2005 that ATP released centrally during hypoxia and hypercapnia contributes to the respective ventilatory responses validated a decade-old hypothesis and ignited interest in the potential significance of P2 receptor signaling in central respiratory control. Our objective in this review is to provide a non-specialist overview of ATP signaling from the perspective that it is a three-part system where the net effects are determined by an interaction between the signaling actions of ATP and adenosine at P2 and P1 receptors, respectively, and a family of enzymes (ectonucleotidases) that breakdown ATP into adenosine. We review the rationale for the original interest in P2 signaling in respiratory control, the evolution of this hypothesis, and the mechanisms by which ATP might affect respiratory behaviour. The potential significance of P2 receptor, P1 receptor and ectonucleotidase diversity for the different compartments of the respiratory control system is also considered. We conclude with a look to future questions and technical challenges.