Fig. 1

ATP degradation and migraine relevant signalling via P2X3, ADP-specific P2Y1 and adenosine activated A1 and A2a receptors. Extracellular ATP is degraded by CD39 to ADP and AMP and the latter is transformed to adenosine (ADO) by CD73. In contrast to CD39, neuron-specific NTPDase2 generates ADP. ATP can activate neuronal P2X3 receptors selectively expressed in sensory neurons, whereas ADP activates metabotropic neuronal P2Y1 receptors (probably also the P2Y12/13 subtypes), which in turn depress P2X3 receptor activity, thus completing this regulatory loop. Adenosine activates either inhibitory A1 or excitatory A2a receptors. Red arrows indicate activation while the block stop line shows an inhibitory effect