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Ethanol's effect on intracellular signal pathways in prenatal rat cortical neurons is GABA B1 dependent
Author(s) -
Lee H.Y.,
Li S.P.,
Park M.S.,
Bahk Y.H.,
Chung B.C.,
Kim M.O.
Publication year - 2007
Publication title -
synapse
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.809
H-Index - 106
eISSN - 1098-2396
pISSN - 0887-4476
DOI - 10.1002/syn.20416
Subject(s) - creb , chemistry , microbiology and biotechnology , gabab receptor , protein subunit , baclofen , protein kinase a , receptor , signal transduction , neuroscience , biology , gabaa receptor , kinase , biochemistry , transcription factor , agonist , gene
To confirm the modulation role of GABA B on ethanol' effects, we studied the effects of ethanol on the neuronal intracellular signals, protein kinase A (PKA) and cAMP‐response element binding protein (CREB), by using a system where GABA B1 receptors were specifically knocked down in the in vitro cultivated cortical neurons. The results showed that the PKA α subunit was increased with ethanol treatment, and could be further increased by administering baclofen and phaclofen. By contrast, baclofen and/or phaclofen could decrease ethanol's up‐regulation effects on PKA α subunit expression in primary cultured cortical neurons in which the GABA B1 receptor was specifically knocked down using GABA B1 receptor RNA interference. Furthermore, these effects could lead to changes of phospho (p)‐CREB expression, which showed the same expression pattern as PKA. Finally, we observed changes of GABA B1 , PKA, and p‐CREB distribution within the same neuronal cells. These results showed that the GABA B receptors are critical to ethanol's cellular effects, which occur via modulating the PKA and CREB transcription pathway, and may be an underlying cause of ethanol's effects. Synapse 61:622–628, 2007. © 2007 Wiley‐Liss, Inc.