FACILITATION OF TRANSMITTER RELEASE FROM RAT SYMPATHETIC NEURONS VIA PRESYNAPTIC P2Y sub(1) RECEPTORS

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 apositive 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 P2Y sub(12) and pertussis toxin-sensitive G proteins (Lechner et al. 2004). In sympathetic neurons, receptors coupled to Gq type G proteins and PLC, such as B sub(2) bradykinin and M1 muscarinic receptors, mediate an inhibition of KCNQ channels (Delmas et al. 2005). We found out that presynaptic P2Y sub(1) receptors mediate a facilitation of transmitter release from sympathetic nerve terminals via PLC. The present study provides the first evidence for a facilitatory P2Y receptor, in sympathetic neurons. Since P2Y sub(1) antagonists are being developed as antithrombotics, this mechanism can be expected to contribute to their pharmacodynamic profile, in particular with respect to the vascular tone.