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Ifenprodil restores GDNF‐evoked Ca 2+ signalling and Na + /K + ‐ATPase expression in inflammation‐pretreated astrocytes
Author(s) -
Lundborg Christopher,
Westerlund Anna,
Björklund Ulrika,
Biber Björn,
Hansson Elisabeth
Publication year - 2011
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2011.07465.x
Subject(s) - glial cell line derived neurotrophic factor , ifenprodil , neuroprotection , neurotrophic factors , nmda receptor , astrocyte , receptor , neuroglia , pharmacology , glutamate receptor , inflammation , chemistry , neuroscience , endocrinology , medicine , biology , biochemistry , central nervous system
J. Neurochem. (2011) 119 , 686–696. Abstract 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 Ca 2+ transients. This study aimed first to assess intracellular Ca 2+ 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 Ca 2+ 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 Ca 2+ 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.