L-Glutamate and Phorbol Ester Stimulate The Release of Secretory Amyloid Precursor Protein from Rat Cortical Synaptosomes
Treatment of rat cortical synaptosomes with micromolar concentrations of L-glutamate stimulated the release of the secreted form of amyloid precursor protein in a concentration-dependent, however biphasic manner as assayed by semiquantitative Western blot analysis. The secreted amyloid precursor protein released from synaptosomes into the incubation medium was highest in the presence of 500 μM L-glutamate (about 64% over the level assayed in the incubation medium in the absence of any drug). In contrast, direct stimulation of protein kinase C by phorbol-12-myristate-13-acetate resulted in a concentration- independent increase in secretory amyloid precursor protein release by about 100% already detectable at a concentration of 0.1 μM but with no significant change at higher concentrations up to 10 μM. The presented data show that there is a constitutive release of secretory amyloid precursor protein from synaptosomes and suggest that (i) processing of amyloid precursor protein at the synaptic level is controlled by L-glutamate presumably via activation of protein kinase C, and (ii) isolated cortical synaptosomes represent a useful experimental approach to selectively study amyloid precursor protein metabolism at the synaptic level.
KeywordsSecreted amyloid precursor protein synaptosomes glutamate phorbol ester protein kinase C
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