Regulated release of nucleotides and UDP sugars from astrocytoma cells

Novartis Found Symp. 2006;276:73-84; discussion 84-90, 107-12, 275-81.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Adenosine Diphosphate Glucose / metabolism*
  • Animals
  • Astrocytes / cytology
  • Astrocytes / metabolism
  • Astrocytoma / metabolism*
  • Astrocytoma / pathology
  • Endoplasmic Reticulum / metabolism
  • Exocytosis / physiology
  • Glioma / metabolism
  • Glioma / pathology
  • Golgi Apparatus / metabolism
  • Humans
  • Membrane Transport Proteins / metabolism
  • Molecular Structure
  • Nucleotides / chemistry
  • Nucleotides / metabolism*
  • Thrombin / metabolism
  • Tumor Cells, Cultured

Substances

  • Membrane Transport Proteins
  • Nucleotides
  • Adenosine Diphosphate Glucose
  • Thrombin