Opposing regulation of amyloid precursor protein by ionotropic and metabotropic glutamate receptors.
The effects of the ionotropic glutamate receptor (iGluR) selective agonist N-methyl-D-aspartate (NMDA) on amyloid precursor protein (APP) levels were investigated in primary cultures of rat cerebellar granule cells. Both immunocytochemistry and immunoblotting techniques showed increased APP levels 4 h after a 15 min pulse with NMDA. This effect was completely prevented by incubating the neurones in the presence of the selective metabotropic GluR (mGluR) agonist 1S,3R-ACPD. This phenomenon was related, in terms of doses and time, with the observed 1S,3R-ACPD-mediated protection on NMDA-induced granule cell death. Our findings indicate that APP metabolism is differentially regulated by the stimulation of various GluR subtypes. The GluR-mediated changes in APP content might participate in the control of neuronal viability.
Valerio
A
A
Department of Biomedical Sciences and Biotechnologies, University of Brescia School of Medicine, Italy.
Alberici
A
A
Paterlini
M
M
Grilli
M
M
Galli
P
P
Pizzi
M
M
Memo
M
M
Spano
P
P
D016564:Amyloid beta-Protein Precursor / Q000187:drug effects*; D000818:Animals; D000906:Antibodies; D002478:Cells, Cultured; D002531:Cerebellum / Q000187:drug effects*; D015151:Immunoblotting; D007150:Immunohistochemistry; D016202:N-Methylaspartate / Q000494:pharmacology*; D051381:Rats; D011919:Rats, Inbred Strains; D018094:Receptors, Metabotropic Glutamate / Q000187:drug effects*
D016564:Amyloid beta-Protein Precursor; D000906:Antibodies; D018094:Receptors, Metabotropic Glutamate; D016202:N-Methylaspartate