Activation of p44/p42 MAP kinase in striatal neurons via kainate receptorsand PI3 kinase

The members of the mitogen-activated protein (MAP) kinase family - p44/p42 MAP kinase (ERK), c-jun N-terminal kinase (JNK) and p38 MAP kinase (p38) ar e known to be important mediators of the physiological plasticity or neurot oxicity induced in the striatum by activation of ionotropic glutamate recep tors. However, our knowledge of the class of glutamate receptor and the int racellular pathways involved derives totally from studies on embryonic neur ons, where the mechanisms are likely to be totally different from those ope rating in mature neurons. In superfused striatal slices from adult rats, NM DA and kainate, but not AMPA. were found to activate ERK. No activation of p38 or JNK was detected following treatment with any ionotropic glutamate r eceptor agonist. The activation of ERK by kainate was blocked by the ERK ki nase (MEK) inhibitor PD98059, and the PI3 kinase inhibitor wortmannin. but not by the p38 MAP kinase inhibitor SB203580. This provides evidence for a novel pathway linking striatal kainate receptors to ERK activation via PI3 kinase and MEK. (C) 2001 Published by Elsevier Science B.V.