ATP is a mediator of chemosensory transduction in the central nervous system

Extracellular signalling by the purine nucleotide ATP has long been associated with sensory function(1-8). In the periphery, ATP mediates nociception(3-5), mechanosensitivity(3,6), thermal sensitivity(7) and O-2 chemosensitivity(8). These processes share a common mechanism that involves the release of ATP to excite afferent fibres via activation of ionotropic P2X and/or metabotropic P2Y receptors. Chemosensors located in the brainstem are crucial for the maintenance of physiological levels of blood gases through the regulation of breathing(9-11). Here we show that an increase in p(CO 2) in the arterial blood triggers the immediate release of ATP from three chemosensitive regions located on the ventral surface of the medulla oblongata. Blockade of ATP receptors at these sites diminishes the chemosensory control of breathing, suggesting that ATP release constitutes a key step in central chemosensory transduction. These new data suggest that ATP, a phylogenetically ancient, unique and simple molecule, has been widely used in the evolution of afferent systems to mediate distinct forms of sensory transduction not only in the periphery but also within the central nervous system.