P2 receptors for purines and pyrimidines are divided into 7 P2X and 8 P2Y receptors (Abbracchio et al. 2006). Noradrenaline (NA) and ATP are the predominant neurotransmitters in the sympathetic nervous system. In rat superior cervical ganglion (SCG) neurons, endogenous ATP activates presynaptic P2X receptors and thereby mediates a positive feedback regulation of NA release (Boehm 1999). In addition, endogenous ADP mediates a feedback inhibition of NA release, through an inhibition of voltage activated calcium channels (VACCs) most likely via P2Y12 and pertussis toxin-sensitive G proteins (Lechner et al. 2004). In sympathetic neurons, receptors coupled to Gq type G proteins and PLC, such as B2 bradykinin and M1 muscarinic receptors, mediate an inhibition of KCNQ channels (Delmas et al. 2005). We found out that presynaptic P2Y1 receptors mediate a facilitation of transmitter release from sympathetic nerve terminals via PLC. The present study provides the fi rst evidence for a facilitatory P2Y receptor, in sympathetic neurons. Since P2Y1 antagonists are being developed as antithrombotics, this mechanism can be expected to contribute to their pharmacodynamic profi le, in particular with respect to the vascular tone.
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