Release of Alzheimer amyloid precursor derivatives stimulated by activation of muscarinic acetylcholine receptors.
Altered processing of the amyloid precursor protein (APP) is a central event in the formation of amyloid deposits in the brains of individuals with Alzheimer's disease. To investigate whether cellular APP processing is controlled by cell-surface neurotransmitter receptors, human embryonic kidney (293) cell lines were transfected with the genes for human brain muscarinic acetylcholine receptors. Stimulation of m1 and m3 receptor subtypes with carbachol increased the basal release of APP derivatives within minutes of treatment, indicating that preexisting APP is released in response to receptor activation. Receptor-activated APP release was blocked by staurosporine, suggesting that protein kinases mediate neurotransmitter receptor-controlled APP processing.
Nitsch
R M
RM
Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge 02139.
Slack
B E
BE
Wurtman
R J
RJ
Growdon
J H
JH
D000470:Alkaloids / Q000494:pharmacology; D000544:Alzheimer Disease / Q000378:metabolism*; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism*; D001285:Atropine / Q000494:pharmacology; D015153:Blotting, Western; D001923:Brain Chemistry; D002217:Carbachol / Q000494:pharmacology; D002460:Cell Line; D004622:Embryo, Mammalian; D006801:Humans; D007668:Kidney; D007700:Kinetics; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D011976:Receptors, Muscarinic / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D019311:Staurosporine; D014162:Transfection
D000470:Alkaloids; D016564:Amyloid beta-Protein Precursor; D011976:Receptors, Muscarinic; D001285:Atropine; D002217:Carbachol; D011493:Protein Kinase C; D019311:Staurosporine