PMID- 16621159 OWN - NLM STAT- MEDLINE DCOM- 20061002 LR - 20191210 IS - 0197-0186 (Print) IS - 0197-0186 (Linking) VI - 49 IP - 4 DP - 2006 Sep TI - Modulation of NMDA receptors by AKT kinase. PG - 351-8 AB - The aim of the present work was to assess whether Akt modulates NMDA receptor function in cerebellar neurons in culture. Forskolin increases cAMP and activates Akt and NMDA receptors. In neurons treated with forskolin, intracellular calcium increased to 296 +/- 38% and this was completely prevented by inhibition of Akt. This indicates that, in these neurons, cAMP modulates NMDA receptors via Epac and Akt. Brain derived neurotrophic factor (BDNF) increases phosphorylation (and activity) of Akt to 350 +/- 60% of basal and also potentiates the increase of calcium and in cGMP induced by NMDA. BDNF-induced potentiation of NMDA receptor function is completely prevented by inhibition of PI3 kinase or of Akt. This indicates that BDNF modulates NMDA receptor function via PI3 kinase and Akt. Activation of NMDA receptors also leads to phosphorylation and activation of Akt which, in turn, potentiates NMDA receptor activation. The results reported indicate that when Akt activity increases the activation of NMDA receptors by its agonists also increases. Akt may play important roles in the modulation of NMDA receptor responses by other neurotransmitters and modulators and in the adaptation of NMDA receptor function to the physiological environmental conditions. FAU - Sanchez-Perez, Ana Maria AU - Sanchez-Perez AM AD - Laboratory of Neurobiology, Centro de Investigacion Principe Felipe, Valencia, Spain. FAU - Llansola, Marta AU - Llansola M FAU - Felipo, Vicente AU - Felipo V LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20060418 PL - England TA - Neurochem Int JT - Neurochemistry international JID - 8006959 RN - 0 (Brain-Derived Neurotrophic Factor) RN - 0 (Enzyme Inhibitors) RN - 0 (Excitatory Amino Acid Agonists) RN - 0 (NR1 NMDA receptor) RN - 0 (Phosphoinositide-3 Kinase Inhibitors) RN - 0 (Receptors, N-Methyl-D-Aspartate) RN - 1F7A44V6OU (Colforsin) RN - 6384-92-5 (N-Methylaspartate) RN - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt) RN - H2D2X058MU (Cyclic GMP) RN - SY7Q814VUP (Calcium) SB - IM MH - Animals MH - Brain-Derived Neurotrophic Factor/pharmacology MH - Calcium/metabolism MH - Cells, Cultured MH - Cerebellum/cytology/drug effects/enzymology MH - Colforsin/pharmacology MH - Cyclic GMP/chemistry/metabolism MH - Drug Synergism MH - Enzyme Activation/physiology MH - Enzyme Inhibitors/pharmacology MH - Excitatory Amino Acid Agonists/pharmacology MH - Immunoblotting MH - Immunoprecipitation MH - N-Methylaspartate/pharmacology MH - Neurons/drug effects/enzymology/metabolism MH - Phosphoinositide-3 Kinase Inhibitors MH - Phosphorylation MH - Proto-Oncogene Proteins c-akt/antagonists & inhibitors/*physiology MH - Rats MH - Rats, Wistar MH - Receptors, N-Methyl-D-Aspartate/*drug effects/metabolism EDAT- 2006/04/20 09:00 MHDA- 2006/10/03 09:00 CRDT- 2006/04/20 09:00 PHST- 2005/10/18 00:00 [received] PHST- 2006/02/01 00:00 [revised] PHST- 2006/02/20 00:00 [accepted] PHST- 2006/04/20 09:00 [pubmed] PHST- 2006/10/03 09:00 [medline] PHST- 2006/04/20 09:00 [entrez] AID - S0197-0186(06)00097-0 [pii] AID - 10.1016/j.neuint.2006.02.005 [doi] PST - ppublish SO - Neurochem Int. 2006 Sep;49(4):351-8. doi: 10.1016/j.neuint.2006.02.005. Epub 2006 Apr 18.