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Prostaglandins stimulate calcium-dependent glutamate release in astrocytes

Author

Listed:
  • Paola Bezzi

    (Institute of Pharmacological Sciences, University of Milan)

  • Giorgio Carmignoto

    (University of Padova)

  • Lucia Pasti

    (University of Padova)

  • Sabino Vesce

    (Institute of Pharmacological Sciences, University of Milan)

  • Daniela Rossi

    (Institute of Pharmacological Sciences, University of Milan)

  • Barbara Lodi Rizzini

    (Institute of Pharmacological Sciences, University of Milan)

  • Tullio Pozzan

    (University of Padova)

  • Andrea Volterra

    (Institute of Pharmacological Sciences, University of Milan)

Abstract

Astrocytes in the brain form an intimately associated network with neurons. They respond to neuronal activity and synaptically released glutamate by raising intracellular calcium concentration ([Ca2+]i)1,2 which could represent the start of back-signalling to neurons3,4,5. Here we show that coactivation of the AMPA/kainate and metabotropic glutamate receptors (mGluRs) on astrocytes stimulates these cells to release glutamate through a Ca2+-dependent process mediated by prostaglandins. Pharmacological inhibition of prostaglandin synthesis prevents glutamate release, whereas application of prostaglandins (in particular PGE2) mimics and occludes the releasing action of GluR agonists. PGE2 promotes Ca2+-dependent glutamate release from cultured astrocytes and also from acute brain slices under conditions that suppress neuronal exocytotic release. When applied to the CA1 hippocampal region, PGE2 induces increases in [Ca2+]i both in astrocytes and in neurons. The [Ca2+]i increase in neurons is mediated by glutamate released from astrocytes, because it is abolished by GluR antagonists. Our results reveal a new pathway of regulated transmitter release from astrocytes and outline the existence of an integrated glutamatergic cross-talk between neurons and astrocytes in situ that may play critical roles in synaptic plasticity and in neurotoxicity.

Suggested Citation

  • Paola Bezzi & Giorgio Carmignoto & Lucia Pasti & Sabino Vesce & Daniela Rossi & Barbara Lodi Rizzini & Tullio Pozzan & Andrea Volterra, 1998. "Prostaglandins stimulate calcium-dependent glutamate release in astrocytes," Nature, Nature, vol. 391(6664), pages 281-285, January.
    • Handle: RePEc:nat:nature:v:391:y:1998:i:6664:d:10.1038_34651
    DOI: 10.1038/34651
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    Cited by:

    1. Marta Gómez-Gonzalo & Gabriele Losi & Angela Chiavegato & Micaela Zonta & Mario Cammarota & Marco Brondi & Francesco Vetri & Laura Uva & Tullio Pozzan & Marco de Curtis & Gian Michele Ratto & Giorgio , 2010. "An Excitatory Loop with Astrocytes Contributes to Drive Neurons to Seizure Threshold," PLOS Biology, Public Library of Science, vol. 8(4), pages 1-19, April.
    2. Vendula Rusnakova & Pavel Honsa & David Dzamba & Anders Ståhlberg & Mikael Kubista & Miroslava Anderova, 2013. "Heterogeneity of Astrocytes: From Development to Injury – Single Cell Gene Expression," PLOS ONE, Public Library of Science, vol. 8(8), pages 1-15, August.
    3. Shengli Guo & Jun Tang & Jun Ma & Chunni Wang, 2017. "Autaptic Modulation of Electrical Activity in a Network of Neuron-Coupled Astrocyte," Complexity, Hindawi, vol. 2017, pages 1-13, June.

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