ALPHA-AMINO-3-HYDROXY-5-METHYL-4-ISOXAZOLEPROPIONIC ACID, BUT NOT N-METHYL-D-ASPARTATE, ACTIVATES MITOGEN-ACTIVATED PROTEIN-KINASE THROUGH G-PROTEIN BETA-GAMMA-SUBUNITS IN RAT CORTICAL-NEURONS

alpha-Amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor channels play important roles in plasticity, neurotransmission, and neurotoxicity in the central nervous system, AMPA, but not N-methyl-D-aspartate (NMDA), receptor signaling in rat cortical neurons was found to involve a G-protein coupled to a protein kinase cascade, While both NMDA and AMPA activated P-42 mitogen-activated protein kinase (MAPK) in neurons, only AMPA-induced MAPK was inhibited by pertussis toxin, AMPA, but not NMDA, caused an association of a G-protein beta subunit with a Ras, Raf kinase, and MAP/ERK kinase (MEK)-1 complex, The evidence indicates that AMPA triggers MAPK activation via a novel mechanism in which G-protein beta gamma dimers released from G alpha bind to a Ras protein complex causing the activation of Ras, Raf kinase, MEK-1, and finally MAPK.