title: Facilitation of transmitter release from rat sympathetic neurons via presynaptic P2Y(1)  receptors.
abstract: OBJECTIVE
  P2Y(1) , P2Y(2) , P2Y(4) , P2Y(12) and P2Y(13) receptors for nucleotides have been reported to mediate presynaptic inhibition, but unequivocal evidence for facilitatory presynaptic P2Y receptors is not available. The search for such receptors was the purpose of this study.
  
  
  METHODS
  In primary cultures of rat superior cervical ganglion neurons and in PC12 cell cultures, currents were recorded via the perforated patch clamp technique, and the release of [(3) H]-noradrenaline was determined.
  
  
  RESULTS
  ADP, 2-methylthio-ATP and ATP enhanced stimulation-evoked (3) H overflow from superior cervical ganglion neurons, treated with pertussis toxin to prevent the signalling of inhibitory G proteins. This effect was abolished by P2Y(1) antagonists and by inhibition of phospholipase C, but not by inhibition of protein kinase C or depletion of intracellular Ca(2+) stores. ADP and a specific P2Y(1) agonist caused inhibition of Kv7 channels, and this was prevented by a respective antagonist. In neurons not treated with pertussis toxin, (3) H overflow was also enhanced by a specific P2Y(1) agonist and by ADP, but only when the P2Y(12) receptors were blocked. ADP also enhanced K(+) -evoked (3) H overflow from PC12 cells treated with pertussis toxin, but only in a clone expressing recombinant P2Y(1) receptors.
  
  
  CONCLUSIONS
  These results demonstrate that presynaptic P2Y(1) receptors mediate facilitation of transmitter release from sympathetic neurons most likely through inhibition of Kv7 channels.
authors.affiliation: Department of Neurophysiology and Pharmacology, Center of Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.
authors.forename: Giri K
authors.initials: GK
authors.lastname: Chandaka
authors.forename: Isabella
authors.initials: I
authors.lastname: Salzer
authors.forename: Helmut
authors.initials: H
authors.lastname: Drobny
authors.forename: Stefan
authors.initials: S
authors.lastname: Boehm
authors.forename: Klaus W
authors.initials: KW
authors.lastname: Schicker
mesh_terms: D000244:Adenosine Diphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000831:Animals, Newborn; D018929:Cell Culture Techniques; D003001:Cloning, Molecular; D004558:Electric Stimulation; D049452:Green Fluorescent Proteins / Q000235:genetics; D051656:KCNQ Potassium Channels / Q000037:antagonists & inhibitors; D020714:Maximum Tolerated Dose; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D018377:Neurotransmitter Agents / Q000378:metabolism*; D009638:Norepinephrine / Q000378:metabolism*; D016716:PC12 Cells; D018408:Patch-Clamp Techniques; D037342:Pertussis Toxin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017661:Receptors, Presynaptic / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D058472:Receptors, Purinergic P2Y1 / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D017783:Superior Cervical Ganglion / Q000187:drug effects / Q000378:metabolism*; D009435:Synaptic Transmission / Q000187:drug effects; D013873:Thionucleotides / Q000494:pharmacology
chemical_list: D051656:KCNQ Potassium Channels; D018377:Neurotransmitter Agents; D017661:Receptors, Presynaptic; D058472:Receptors, Purinergic P2Y1; D013873:Thionucleotides; D049452:Green Fluorescent Proteins; C002480:methylthio-ADP; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D037342:Pertussis Toxin; D009638:Norepinephrine; C008501:2-methylthio-ATP