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Protein kinase C activity blocks neuropeptide Y‐mediated inhibition of glutamate release and contributes to excitability of the hippocampus in status epilepticus
Author(s) -
Silva Ana P.,
Lourenco Joana,
Xapelli Sara,
Ferreira Raquel,
Kristiansen Heidi,
Woldbye David P. D.,
Oliveira Catarina R.,
Malva Joao O.
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.06-6163com
Subject(s) - glutamate receptor , kainate receptor , protein kinase c , ampa receptor , neuropeptide y receptor , nmda receptor , long term potentiation , chemistry , pharmacology , biology , receptor , neuroscience , microbiology and biotechnology , neuropeptide , phosphorylation , biochemistry
The unbalanced excitatory/inhibitory neurotransmitter function in the neuronal network afflicted by seizures is the main biochemical and biophysical hallmark of epilepsy. The aim of this work was to identify changes in the signaling mechanisms associated with neuropeptide Y (NPY)‐mediated inhibition of glutamate release that may contribute to hyperexcitabil‐ity. Using isolated rat hippocampal nerve terminals, we showed that the KCl‐evoked glutamate release is inhibited by NPY Y 2 receptor activation and is potentiated by the stimulation of protein kinase C (PKC). Moreover, we observed that immediately after status epilepticus (6 h postinjection with kainate, 10 mg/kg), the functional inhibition of glutamate release by NPY Y 2 receptors was transiently blocked concomitantly with PKC hyperacti‐vation. The pharmacological blockade of seizure‐activated PKC revealed again the Y 2 receptor‐mediated inhibition of glutamate release. The functional activity of PKC immediately after status epilepticus was as‐sessed by evaluating phosphorylation of the AMPA receptor subunit GluRl (Ser‐831), a substrate for PKC. Moreover, NPY‐stimulated [ 35 S]GTPγS autoradiographic binding studies indicated that the common target for Y 2 receptor and PKC on the inhibition/ potentiation of glutamate release was located downstream of the Y 2 receptor, or its interacting G‐protein, and involves voltage‐gated calcium channels.—Silva, A. P., Lourenco, J., Xapelli, S., Ferreira, R., Kristiansen, H., Woldbye, D. P. D., Oliveira, C. R., Malva, J. O. Protein kinase C activity blocks neuropeptide Y‐mediated inhibition of glutamate release and contributes to excitability of the hippocampus in status epilepticus. FASEB J. 21, 671–681 (2007)