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GPR40 activation leads to CREB and ERK phosphorylation in primary cultures of neurons from the mouse CNS and in human neuroblastoma cells
Author(s) -
Zamarbide Marta,
EtayoLabiano Iñigo,
Ricobaraza Ana,
MartínezPinilla Eva,
Aymerich María S.,
Luis Lanciego José,
PérezMediavilla Alberto,
Franco Rafael
Publication year - 2014
Publication title -
hippocampus
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.767
H-Index - 155
eISSN - 1098-1063
pISSN - 1050-9631
DOI - 10.1002/hipo.22263
Subject(s) - creb , free fatty acid receptor 1 , phosphorylation , neuroscience , hippocampal formation , agonist , mapk/erk pathway , receptor , biology , microbiology and biotechnology , chemistry , biochemistry , transcription factor , gene
GPR40, the free fatty acid receptor 1, is expressed strongly in the primate pancreas and brain. While the role of pancreatic GPR40 in glucose homeostasis has been extensively studied, the absence of this G‐protein‐coupled receptor from the brain of rodents has hampered studies into its role in the central nervous system. However, we found intense GPR40 mRNA expression by in situ hybridization in mouse hippocampal and motor cortex neurons. Furthermore, in a neuroblastoma cell GPR40 was activated by docosahexaenoic acid and selective agonists, yet not by palmitic acid. Significantly, the activation of GPR40 provoked the phosphorylation of the cAMP response element‐binding protein, CREB. The receptor was also functional in primary cultures of murine neurons, in which its activation by a selective agonist produced the phosphorylation of CREB and of extracellular signal‐regulated kinases, ERK1/2. These results suggest that mice represent a suitable model for elucidating the role of GPR40 in brain function. © 2014 Wiley Periodicals, Inc.