UTP evokes noradrenaline release from rat sympathetic neurons by activation of protein kinase C.
The pathway involved in UTP-evoked noradrenaline release was investigated in cultures of rat superior cervical ganglia. Northern blots revealed an age-related increase in levels of mRNA for P2Y6 receptors in cultures obtained at postnatal days 1 and 5, respectively, but no change in transcripts for P2Y1 and P2Y2. Likewise, UTP-evoked overflow of previously incorporated [(3)H]noradrenaline was six-fold higher in neurons obtained at postanatal day 5. Various protein kinase C inhibitors diminished UTP-, but not electrically, induced tritium overflow by > 70%, as did down-regulation of protein kinase C by 24 h exposure to phorbol ester. beta-Phorbol-12,13-dibutyrate and dioctanoylglycerol caused concentration-dependent increases in [(3)H] outflow of up to 6% of total radioactivity, and the secretagogue actions of these agents were reduced in the presence of protein kinase C inhibitors and in neurons pretreated with phorbol ester. Overflow evoked by dioctanoylglycerol was attenuated in the absence of extracellular Ca(2+) and in the presence of tetrodotoxin or Cd(2+). In addition to triggering tritium overflow, UTP reduced currents through muscarinic K(+) channels which, however, were not affected by phorbol esters. This action of UTP was not altered by protein kinase C inhibitors. These results indicate that P2Y6 receptors mediate UTP-evoked noradrenaline release from rat sympathetic neurons via activation of protein kinase C, but not inhibition of K(M) channels.
Vartian
N
N
Institute of Pharmacology, University of Vienna, Vienna, Austria.
Moskvina
E
E
Scholze
T
T
Unterberger
U
U
Allgaier
C
C
Boehm
S
S
D000818:Animals; D000831:Animals, Newborn; D015152:Blotting, Northern; D002104:Cadmium / Q000494:pharmacology; D002118:Calcium / Q000494:pharmacology; D002478:Cells, Cultured; D004553:Electric Conductivity; D004558:Electric Stimulation; D004789:Enzyme Activation / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000494:pharmacology; D009474:Neurons / Q000502:physiology*; D009638:Norepinephrine / Q000378:metabolism*; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000502:physiology; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018048:Receptors, Purinergic P2 / Q000235:genetics; D017783:Superior Cervical Ganglion / Q000737:chemistry*; D013779:Tetrodotoxin / Q000494:pharmacology; D014316:Tritium; D014544:Uridine Triphosphate / Q000494:pharmacology*
D004791:Enzyme Inhibitors; D015221:Potassium Channels; D012333:RNA, Messenger; D018048:Receptors, Purinergic P2; C099845:purinoceptor P2Y6; D002104:Cadmium; D014316:Tritium; D015240:Phorbol 12,13-Dibutyrate; D013779:Tetrodotoxin; D011493:Protein Kinase C; D002118:Calcium; D014544:Uridine Triphosphate; D009638:Norepinephrine