Abstract:

Beyond its role in energy storage, adenosine 5í-triphosphate (ATP) was recognized in the early 1970s to be an extracellular signaling molecule. In addition to ATP being demonstrated to act as a transmitter in non-adrenergic, non-cholinergic nerves, it was also recognized as a co-transmitter in nerves in both peripheral and central nervous systems. Receptors for this purine are widely expressed on non-neuronal as well as nerve cells, and can be involved in signal transduction relating to blood pressure homeostasis, sensation and pain. Interestingly, the afferent C-fibers in the vagus nerve innervating the airways that can evoke coughing express P2X3 receptors that can be activated by ATP released into the airways. Thus, P2X3-receptor activation might enhance responsiveness to a broad range of stimuli mediating cough hypersensitivity. Indeed, clinically, a P2X3 receptor antagonist was found to elicit significant reductions in daytime cough frequency and statistically significant improvements in patient-reported outcomes of cough. Additional potential clinical indications for purinergic receptor antagonists are currently being explored.