Regulated Release of Nucleotides and UDP Sugars from Astrocytoma Cells

  1. Derek J. Chadwick Organizer and
  2. Jamie Goode
  1. Eduardo Lazarowski

Published Online: 7 OCT 2008

DOI: 10.1002/9780470032244.ch7

Purinergic Signalling in Neuron-Glia Interactions: Novartis Foundation Symposium 276

Purinergic Signalling in Neuron-Glia Interactions: Novartis Foundation Symposium 276

How to Cite

Lazarowski, E. (2006) Regulated Release of Nucleotides and UDP Sugars from Astrocytoma Cells, in Purinergic Signalling in Neuron-Glia Interactions: Novartis Foundation Symposium 276 (eds D. J. Chadwick and J. Goode), John Wiley & Sons, Ltd, Chichester, UK. doi: 10.1002/9780470032244.ch7

Author Information

  1. University of North Carolina at Chapel Hill, Cystic Fibrosis/Pulmonary Research & Treatment Center, 7017 Thurston-Bowles Building, CB 7248, Chapel Hill, NC 27599-7248, USA

Publication History

  1. Published Online: 7 OCT 2008
  2. Published Print: 21 APR 2006

Book Series:

  1. Novartis Foundation Symposia

Book Series Editors:

  1. Novartis Foundation

ISBN Information

Print ISBN: 9780470018606

Online ISBN: 9780470032244

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Keywords:

  • nucleotide release and UDP-glucose;
  • UDP-glucose in metabolic reactions;
  • purinergic receptors in astrocytes;
  • apyrase-sensitive inositol phosphate formation;
  • uridine nucleotide and nucleotide-sugar accumulation

Summary

ATP is co-stored in neurosecretory vesicles together with aminergic compounds and is released from neural cells and synaptic terminals via regulated exocytosis. ATP also is released from non-neuronal cells including astrocytes and astrocyte-like cell lines. However, the mechanism(s) involved in ATP release from astrocytes and other non-secretory cells remains unclear. ATP release from primary astrocytes, astrocytoma, and glioma cells is accompanied by enhanced accumulation of extracellular UTP, and we have recently discovered that in addition to adenine and uridine nucleotides, astrocytoma cells release UDP-glucose. It has been illustrated that agonists that promote Ca2+mobilization, e.g. thrombin, promote robust release of ATP from 1321N1 astrocytoma cells. Agonist-promoted release of ATP from 1321N1 astrocytoma cells also results in the release of UDP-glucose but, unlike fast hydrolysable ATP, UDP-glucose was hydrolysed at a markedly slow rate. Since UDP-sugars and ATP are concentrated up to 20 times in the lumen of the secretory pathway to serve as substrates for glycosyl transferase and phosphorylation reactions, respectively, we propose that both constitutive and regulated release of nucleotides and nucleotide-sugars from astrocytes involves a vesicular mechanism. Observation that adenine nucleotides, uridine nucleotides, and UDP-sugars are released from both resting and stimulated astrocytes provides support for the physiological significance of nucleotide- and UDP-sugar-sensing P2Y receptors in the brain. These findings also suggest that slow hydrolysable UDP-glucose may accomplish long lasting signalling on P2Y14 receptors expressed in astrocytes.