OPPOSING REGULATION OF AMYLOID PRECURSOR PROTEIN BY IONOTROPIC AND METABOTROPIC GLUTAMATE RECEPTORS

THE effects of the ionotropic glutamate receptor (iGluR) selective ago nist N-methyl-D-aspartate (NMDA) on amyloid precursor protein (APP) le vels were investigated in primary cultures of rat cerebellar granule c ells. Both immunocytochemistry and immunoblotting techniques showed in creased APP levels 4 h after a 15 min pulse with NMDA. This effect was completely prevented by incubating the neurones in the presence of th e selective metabotropic GluR (mGluR) agonist 1S,3R-ACPD. This phenome non was related, in terms of doses and time, with the observed 1S,3R-A CPD-mediated protection on NMDA-induced granule cell death. Our findin gs indicate that APP metabolism is differentially regulated by the sti mulation of various GluR subtypes. The GluR-mediated changes in APP co ntent might participate in the control of neuronal viability.