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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

Authors

  • Marta Zamarbide,

    1. Neurosciences Division, Center for Applied Medical Research-CIMA, University of Navarra, Pamplona, Spain
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  • Iñigo Etayo-Labiano,

    1. Neurosciences Division, Center for Applied Medical Research-CIMA, University of Navarra, Pamplona, Spain
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  • Ana Ricobaraza,

    1. Neurosciences Division, Center for Applied Medical Research-CIMA, University of Navarra, Pamplona, Spain
    2. Laboratoire de Neurobiologie, ESPCI-ParisTech, Paris, France
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  • Eva Martínez-Pinilla,

    1. Neurosciences Division, Center for Applied Medical Research-CIMA, University of Navarra, Pamplona, Spain
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  • María S. Aymerich,

    1. Neurosciences Division, Center for Applied Medical Research-CIMA, University of Navarra, Pamplona, Spain
    2. Department of Biochemistry and Genetic, University of Navarra, Pamplona, Spain
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  • José Luis Lanciego,

    1. Neurosciences Division, Center for Applied Medical Research-CIMA, University of Navarra, Pamplona, Spain
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  • Alberto Pérez-Mediavilla,

    Corresponding author
    1. Neurosciences Division, Center for Applied Medical Research-CIMA, University of Navarra, Pamplona, Spain
    2. Department of Biochemistry and Genetic, University of Navarra, Pamplona, Spain
    • Correspondence to: Alberto Pérez-Mediavilla, Neurosciences Division, Center for Applied Medical Research – CIMA, University of Navarra, Pio XII 55, 31008 Pamplona, Spain. E-mail: lamediav@unav.es

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  • Rafael Franco

    1. Neurosciences Division, Center for Applied Medical Research-CIMA, University of Navarra, Pamplona, Spain
    2. Laboratoire de Neurobiologie, ESPCI-ParisTech, Paris, France
    3. Department of Biochemistry and Molecular Biology, University of Barcelona, Spain
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  • A.P.-M. and R.F. contributed equally to this work.

ABSTRACT

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.

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