title: GPR40 activation leads to CREB and ERK phosphorylation in primary cultures of neurons from the mouse CNS and in human neuroblastoma cells.
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.
authors.affiliation: Neurosciences Division, Center for Applied Medical Research-CIMA, University of Navarra, Pamplona, Spain.
authors.forename: Marta
authors.initials: M
authors.lastname: Zamarbide
authors.forename: Iñigo
authors.initials: I
authors.lastname: Etayo-Labiano
authors.forename: Ana
authors.initials: A
authors.lastname: Ricobaraza
authors.forename: Eva
authors.initials: E
authors.lastname: Martínez-Pinilla
authors.forename: María S
authors.initials: MS
authors.lastname: Aymerich
authors.forename: José
authors.initials: J
authors.lastname: Luis Lanciego
authors.forename: Alberto
authors.initials: A
authors.lastname: Pérez-Mediavilla
authors.forename: Rafael
authors.initials: R
authors.lastname: Franco
mesh_terms: D000818:Animals; D001565:Benzoates / Q000494:pharmacology; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000166:cytology; D017362:Cyclic AMP Response Element-Binding Protein / Q000378:metabolism*; D006624:Hippocampus / Q000166:cytology; D006801:Humans; D008744:Methylamines / Q000494:pharmacology; D051379:Mice; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D009447:Neuroblastoma / Q000473:pathology; D009474:Neurons / Q000187:drug effects / Q000378:metabolism*; D019308:Palmitic Acid / Q000494:pharmacology; D010766:Phosphorylation; D061251:Primary Cell Culture; D011422:Propionates / Q000494:pharmacology; D011499:Protein Processing, Post-Translational; D011743:Pyrimidines / Q000494:pharmacology; D012333:RNA, Messenger / Q000096:biosynthesis; D043562:Receptors, G-Protein-Coupled / Q000819:agonists / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*
chemical_list: D001565:Benzoates; C115163:CREB1 protein, human; C492004:Creb1 protein, mouse; D017362:Cyclic AMP Response Element-Binding Protein; C473034:FFAR1 protein, human; C473036:Ffar1 protein, mouse; C515631:GW1100; C515630:GW9508; D008744:Methylamines; D009419:Nerve Tissue Proteins; D011422:Propionates; D011743:Pyrimidines; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D019308:Palmitic Acid
keywords: CREB phosphorylation; ERK1/2; GPCRs; GPR40; hippocampus