Research Article

Activation of adenosine A2A receptor protects sympathetic neurons against nerve growth factor withdrawal

  1. Servio H. Ramirez1,
  2. Shongshan Fan1,
  3. Casey A. Maguire1,
  4. Seth Perry2,
  5. Kathy Hardiek3,
  6. Vickram Ramkumar4,
  7. Harris A. Gelbard2,
  8. Stephen Dewhurst1,2,5,*,
  9. Sanjay B. Maggirwar1,2

Article first published online: 20 MAY 2004

DOI: 10.1002/jnr.20150

Issue

Journal of Neuroscience Research

Journal of Neuroscience Research

Volume 77, Issue 2, pages 258–269, 15 July 2004

Additional Information

How to Cite

Ramirez, S. H., Fan, S., Maguire, C. A., Perry, S., Hardiek, K., Ramkumar, V., Gelbard, H. A., Dewhurst, S. and Maggirwar, S. B. (2004), Activation of adenosine A2A receptor protects sympathetic neurons against nerve growth factor withdrawal. Journal of Neuroscience Research, 77: 258–269. doi: 10.1002/jnr.20150

Author Information

  1. 1

    Department of Microbiology and Immunology, University of Rochester School of Medicine and Dentistry, Rochester, New York

  2. 2

    Interdepartmental Program in Neuroscience, University of Rochester School of Medicine and Dentistry, Rochester, New York

  3. 3

    Department of Pharmacology, Southern Illinois University, Springfield, Illinois

  4. 4

    Prairie Education and Research Cooperative, Springfield, Illinois

  5. 5

    Cancer Center, University of Rochester School of Medicine and Dentistry, Rochester, New York

*Department of Microbiology and Immunology, University of Rochester Medical Center, 601 Elmwood Ave., Box 672 (Room 3-9609), Rochester, NY 14642

Publication History

  1. Issue published online: 14 JUN 2004
  2. Article first published online: 20 MAY 2004
  3. Manuscript Accepted: 9 MAR 2004
  4. Manuscript Revised: 3 MAR 2004
  5. Manuscript Received: 20 NOV 2003

Funded by

  • NIH. Grant Numbers: ROI NS39039, PO1 MH64570, S11 NS43499, T32 AI49815, F31AI10666

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Keywords:

  • superior cervical ganglion;
  • neurotrophin;
  • apoptosis;
  • adenosine receptors;
  • CGS21680

Abstract

Adenosine mediates a range of effects in the central nervous system (CNS), including the promotion of neuronal survival, but its actions on sympathetic neurons are less well characterized. We therefore sought to understand the role of endogenous adenosine in contributing to the survival of neurotrophin-dependent sympathetic neurons. Rat superior cervical ganglion (SCG) cultures were maintained in the continuous presence of nerve growth factor (NGF) and then exposed to adenosine deaminase (ADA), to deplete endogenous adenosine. This resulted in a marked increase in cellular apoptosis, to a level that approximated the effect of NGF withdrawal. Furthermore, the addition of exogenous adenosine to NGF-deprived SCG neurons resulted in enhanced cell survival. Analysis of adenosine receptor (AR) subtypes on these neurons, using real-time RT-PCR and receptor binding analyses, revealed that the A2A receptor was the major subtype present. Accordingly, the A2A receptor agonist CGS21680 significantly reduced both ADA-induced and NGF-withdrawal-induced neuronal apoptosis, whereas the A1 receptor agonist R-PIA had no such effect. The survival-promoting effect of CGS21680 was eliminated when cells were coincubated with a molar excess of an A2A receptor antagonist. Finally, follow-up experiments revealed that CGS21680 prevented the induction of early apoptotic events, such as changes in mitochondrial integrity and caspase activation, and that it also triggered an increase in ERK activation, which was essential for neurotrophin-independent cell survival. Taken together, these findings provide evidence that endogenous adenosine may be important in mediating protection of sympathetic neurons and that it may act via the A2A receptor subtype. © 2004 Wiley-Liss, Inc.

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