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Kainic Acid‐Induced Neurotrophic Activities in Developing Cortical Neurons
Author(s) -
Lee YiHsuan,
Fang KwangMing,
Yang ChuenMao,
Hwang HwaMin,
Chiu ChiTso,
Tsai Wuhong
Publication year - 2000
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 - 10.1046/j.1471-4159.2000.0742401.x
Subject(s) - ampa receptor , kainic acid , calcium in biology , tropomyosin receptor kinase a , microbiology and biotechnology , cnqx , phospholipase c , chemistry , bapta , metabotropic glutamate receptor , neurotrophin , biology , glutamate receptor , medicine , endocrinology , receptor , intracellular , signal transduction , biochemistry
Using primary cultured cortical neurons from embryonic rat brains, we elucidated an α‐amino‐3‐hydroxy‐5‐methyl‐4‐isoxazole propionate (AMPA)/kainic acid (KA) receptor‐mediated neuroprotective mechanism through actions of nerve growth factor (NGF) in developing neurons. Neurotoxicity of KA in early days in vitro neurons was quite low compared with the mature neurons. However, pretreatment with anti‐NGF antibody or TrkA inhibitor AG‐879 profoundly raised KA toxicity. Furthermore, KA stimulation resulted in an increase of TrkA expression and phosphorylation, which was blocked not only by the AMPA/KA receptor antagonist 6‐cyano‐7‐nitroquinoxaline‐2,3‐dione and AG‐879, but also by the phospholipase C inhibitor U73122 and the intracellular calcium chelator BAPTA. A study of polyphosphoinositide turnover showed that KA‐stimulated phospholipase C (PLC) activity was directly triggered by the AMPA/KA receptor activity, but not by the activity of TrkA or other excitatory amino acid receptor subtypes. Sources of KA‐increased intracellular calcium levels were contributed by both extracellular calcium influx and intracellular calcium release and were partially sensitive to guanosine 5′‐ O ‐(2‐thiodiphosphate). These results indicate that in developing cortical neurons, activation of AMPA/KA receptors by KA may induce expression, followed by activation of TrkA via PLC signaling and intracellular calcium elevation and hence increase reception of NGF on KA‐challenged neurons. A G protein‐coupled AMPA/KA receptor may be involved in these metabotropic events for neuronal protection.