The role of P2Y1 receptor signaling in central respiratory control

• We review the role of P2Y1 receptor signaling in central respiratory control.
• P2Y1 receptors do not appear to contribute to the chemosensitivity of RTN neurons.
• P2Y1 receptors in the preBötC appear to attenuate the hypoxic respiratory depression.
• Effects on rhythm are likely mediated by Gαq GPCRs, perhaps via KCNQ, TASK or BK/SK.
• Signaling pathways through which P2Y1 receptors may modulate rhythm are reviewed.

The profile of P2 receptor signaling in respiratory control has increased substantially since the first suggestions more than 15 years ago of roles in central chemoreception and modulating inspiratory motor outflow. Part of this reflects the paradigm shift that glia participate in information processing and that ATP is a major gliotransmitter. P2 receptors are a diverse family. Here, we review ATP signaling in respiratory control, highlighting G-protein coupled P2Y1 receptors that have been a focus of recent work. Despite strong evidence of a role for glia and P2 receptor signaling in the central chemosensitivity mediated by the retotrapezoid nucleus, P2Y1 receptors do not appear to be directly involved. Evidence that central P2 receptors and glia contribute to the hypoxic ventilatory response is compelling and P2Y1 receptors are the strongest candidate. However, functional significance in vivo, details of the signaling pathways and involvement of other receptor subtypes remain important questions.