Ifenprodil restores GDNF-evoked Ca2+ signalling and Na+/K+-ATPase expression in inflammation-pretreated astrocytes
Article first published online: 3 OCT 2011
© 2011 The Authors. Journal of Neurochemistry © 2011 International Society for Neurochemistry
Journal of Neurochemistry
Volume 119, Issue 4, pages 686–696, November 2011
How to Cite
Lundborg, C., Westerlund, A., Björklund, U., Biber, B. and Hansson, E. (2011), Ifenprodil restores GDNF-evoked Ca2+ signalling and Na+/K+-ATPase expression in inflammation-pretreated astrocytes. Journal of Neurochemistry, 119: 686–696. doi: 10.1111/j.1471-4159.2011.07465.x
- Issue published online: 19 OCT 2011
- Article first published online: 3 OCT 2011
- Accepted manuscript online: 29 AUG 2011 12:09PM EST
- Received June 23, 2011; revised manuscript received August 22, 2011; accepted August 22, 2011.
J. Neurochem. (2011) 119, 686–696.
Glial cell line-derived neurotrophic factor (GDNF) plays an important role in neuroinflammatory and neuropathic pain conditions. Astrocytes produce and secrete GDNF, which interacts with its receptors to induce Ca2+ transients. This study aimed first to assess intracellular Ca2+ responses of astrocytes in primary culture when exposed to the neuroprotective and anti-inflammatory peptide GDNF. Furthermore, incubation with the inflammatory inducers lipopolysaccharide (LPS), NMDA, or interleukin 1-β (IL-1β) attenuated the GDNF-induced Ca2+ transients. The next aim was to try to restore the suppressed GDNF responses induced by inflammatory changes in the astrocytes with an anti-inflammatory substance. Ifenprodil, an NMDA receptor antagonist at the NR2B subunit, was tested. It was shown to restore the GDNF-evoked Ca2+ transients and increased the Na+/K+-ATPase expression. Ifenprodil seems to be a potent anti-inflammatory substance for astrocytes which have been pre-activated by inflammatory stimuli.