A.P.-M. and R.F. contributed equally to this work.
GPR40 activation leads to CREB and ERK phosphorylation in primary cultures of neurons from the mouse CNS and in human neuroblastoma cells
Article first published online: 27 FEB 2014
© 2014 Wiley Periodicals, Inc.
Volume 24, Issue 7, pages 733–739, July 2014
How to Cite
Zamarbide, M., Etayo-Labiano, I., Ricobaraza, A., Martínez-Pinilla, E., Aymerich, M. S., Luis Lanciego, J., Pérez-Mediavilla, A. and Franco, R. (2014), GPR40 activation leads to CREB and ERK phosphorylation in primary cultures of neurons from the mouse CNS and in human neuroblastoma cells. Hippocampus, 24: 733–739. doi: 10.1002/hipo.22263
- Issue published online: 19 JUN 2014
- Article first published online: 27 FEB 2014
- Accepted manuscript online: 18 FEB 2014 08:11AM EST
- Manuscript Accepted: 14 FEB 2014
- Manuscript Revised: 5 FEB 2014
- Manuscript Received: 2 OCT 2013
- Foundation for Applied Medical Research (UTE project FIMA), Spain
- Spanish Ministry of Economy and Competitiveness. Grant Number: SAF2012-39875-C02-01
- CREB phosphorylation;
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.