UTP evokes noradrenaline release from rat sympathetic neurons by activation of protein kinase C

• Published in: Journal of neurochemistry Vol. 77; no. 3; pp. 876 - 885
• Main Authors: Vartian, Nina, Moskvina, Eugenia, Scholze, Thomas, Unterberger, Ursula, Allgaier, Clemens, Boehm, Stefan
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.05.2001; Blackwell
• Subjects: Animals; Animals, Newborn; Biological and medical sciences; Blotting, Northern; Cadmium - pharmacology; Calcium - pharmacology; Cells, Cultured; Electric Conductivity; Electric Stimulation; Enzyme Activation - drug effects; Enzyme Inhibitors - pharmacology; Fundamental and applied biological sciences. Psychology; Isolated neuron and nerve. Neuroglia; muscarinic K+ channels; Neurons - physiology; noradrenaline release; Norepinephrine - metabolism; P2Y receptors; Phorbol 12,13-Dibutyrate - pharmacology; Potassium Channels - drug effects; Potassium Channels - physiology; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - metabolism; protein kinase C; rat superior cervical ganglion neurons; Rats; Rats, Sprague-Dawley; Receptors, Purinergic P2 - genetics; RNA, Messenger - analysis; Superior Cervical Ganglion - chemistry; Tetrodotoxin - pharmacology; Tritium; Uridine Triphosphate - pharmacology; uridinetriphosphatase; UTP; Vertebrates: nervous system and sense organs; Spinal cord; Protein kinase C; Rat; Enzyme; Transferases; Rodentia; Central nervous system; P2 Purinergic receptor; Ionic channel; Catecholamine; In vitro; Cholinergic receptor; Vertebrata; Mammalia; Neuron; Spinal ganglion; Norepinephrine; Muscarinic receptor; Potassium
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1046/j.1471-4159.2001.00290.x

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 [3H]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. β‐Phorbol‐12,13‐dibutyrate and dioctanoylglycerol caused concentration‐dependent increases in [3H] 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 Ca2+ and in the presence of tetrodotoxin or Cd2+. 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 KM channels.