The function of a neuron critically depends on the opening and closure of Ca2+ and K+ channels. Voltage-activated Ca2+ channels mediate transmembrane Ca2+ entry in response to membrane depolarization and thereby contribute to transmitter release, whereas K+ channels help to keep the membrane polarized and thus control neuronal excitability. Sympathetic neurons express N-type Ca2+ channels and M-type K+ channels, which both are characterized by their propensity to be inhibited via G protein-coupled receptors. A plethora of transmitters (such as acetylcholine, adenosine, noradrenaline, prostaglandin E2, somatostatin, substance P, vasoactive intestinal polypeptide) act via appropriate receptors to control the gating of one or both of these ion channels in rat superior cervical ganglion (SCG) neurons (Hille, 1994). Filippov et al.(2002) have now added adenine and uridine nucleotides to this growing list of neuromodulators. Extracellular nucleotides exert their effects via ionotropic P2X and metabotropic P2Y receptors. At least seven different P2Y receptors have been identified in mammalian species (P2Y1, 2, 4, 6, 11, 12, 13; Ralevic & Burnstock, 1998; Communi et al., 2001; Hollopeter et al., 2001; Zhang et al., 2001). They are all characterized by a common structural profile with seven putative transmembrane domains typical of G proteincoupled receptors, but display considerable heterogeneity in amino acid sequences. P2Y1, 11, 12 and 13 are activated by adenine nucleotides, whereas P2Y6 is activated by uridine nucleotides. P2Y2 and 4 receptors, in contrast, are sensitive to both adenine and uridine nucleotides. In heterologous expression systems, all P2Y receptor subtypes, with the exception of P2Y12, couple to phospholipase C (PLC) and mediate increases in inositol trisphosphate (IP3; Ralevic & Burnstock, 1998; Communi et al., 2001). P2Y12 and P2Y13 mediate an inhibition of adenylyl cyclase (Hollopeter et al., 2001; Communi et al., 2001).

Transcripts for P2Y1, 2, 6 and 13 are widely distributed in a variety of tissues including the nervous system. P2Y4 and 11, in contrast show a restricted expression pattern that excludes neuronal tissues (Ralevic & Burnstock, 1998; Communi et al., 2001). Finally, P2Y12 was reported to be restricted to blood platelets and to the brain (Hollopeter et al., 2001; Zhang et