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Metabotropic Glutamate Receptors Increase Amyloid Precursor Protein Processing in Astrocytes: Inhibition by Cyclic AMP
Author(s) -
Lee Robert K. K.,
Wurtman Richard J.
Publication year - 1997
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1997.68051830.x
Subject(s) - metabotropic glutamate receptor 1 , metabotropic glutamate receptor , metabotropic glutamate receptor 6 , metabotropic glutamate receptor 5 , protein kinase c , metabotropic glutamate receptor 7 , metabotropic glutamate receptor 4 , metabotropic glutamate receptor 2 , chemistry , biochemistry , metabotropic glutamate receptor 3 , metabotropic receptor , glutamate receptor , microbiology and biotechnology , biology , receptor , signal transduction
Neurotransmitter receptors that increase phosphatidylinositol hydrolysis generate second messengers that activate protein kinase C. Here, we used metabotropic glutamate receptor agonists to increase both phosphatidylinositol hydrolysis and secretion of the soluble extracellular fragment of amyloid precursor protein (APPs) from cortical astrocyte cultures. The increase in APPs secretion was mimicked by direct activation of protein kinase C with phorbol ester and was suppressed by the metabotropic glutamate receptor antagonist l ‐(+)‐2‐amino‐3‐phosphonopropionic acid or by the protein kinase C inhibitor GF109203X. Ionotropic glutamate agonists did not increase APPs secretion. Forskolin or dibutyryl cyclic AMP inhibited the increase in APPs secretion caused by metabotropic glutamate receptor agonists or by phorbol ester treatment but did not affect basal APPs levels. Therefore, glutamatergic agonists that increase protein kinase C activation or decrease cyclic AMP formation may enhance the conversion of full‐length APP to nonamyloidogenic APPs in Alzheimer's disease.