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PMID: 1359534 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Cholinergic agonists and interleukin 1 regulate processing and secretion of the Alzheimer beta/A4 amyloid protein precursor.

Proceedings of the National Academy of Sciences of the United States of America ·Vol. 89 ·No. 21 ·1992-11-01 ·Pages 10075-8

Buxbaum JD, Oishi M, Chen HI, Pinkas-Kramarski R, Jaffe EA, Gandy SE, Greengard P

Abstract

Activation of protein kinase C by phorbol esters is known to accelerate the processing and secretion of the beta/A4 amyloid protein precursor. We have now examined various first messengers that increase protein kinase C activity of target cells for their ability to affect beta/A4 amyloid protein precursor metabolism. Acetylcholine and interleukin 1, which are altered in Alzheimer disease, were shown to increase processing of the beta/A4 amyloid protein precursor via the secretory cleavage pathway. Cholinergic agonists stimulated secretion in human glioma and neuroblastoma cells as well as in PC12 cells transfected with the M1 receptor, while interleukin 1 stimulated secretion in human endothelial and glioma cells.

MeSH Terms
Acetylcholine/pharmacology Amyloid beta-Peptides/biosynthesis,isolation & purification,metabolism Amyloid beta-Protein Precursor/biosynthesis,genetics,isolation & purification Animals Atropine/pharmacology Bethanechol Bethanechol Compounds/pharmacology Carbachol/pharmacology Cell Line Cells, Cultured Chloroquine/pharmacology Dose-Response Relationship, Drug Endothelium, Vascular/drug effects,physiology Humans Interleukin-1/pharmacology Kinetics PC12 Cells Parasympathomimetics/pharmacology Phorbol 12,13-Dibutyrate/pharmacology Protein Kinase C/metabolism Recombinant Proteins/pharmacology Umbilical Veins
Chemicals
Amyloid beta-Peptides Amyloid beta-Protein Precursor Bethanechol Compounds Interleukin-1 Parasympathomimetics Recombinant Proteins Bethanechol Phorbol 12,13-Dibutyrate Atropine Chloroquine Carbachol Protein Kinase C Acetylcholine
Authors & Affiliations
7 authors, click to expand affiliations / ORCID
Buxbaum J D
Laboratory of Molecular and Cellular Neuroscience, Rockefeller University, New York, NY 10021.
Oishi M
Chen H I
Pinkas-Kramarski R
Jaffe E A
Gandy S E
Greengard P
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Article Info
Journal
Proceedings of the National Academy of Sciences of the United States of America
Abbr.
Proc Natl Acad Sci U S A
ISSN
0027-8424
DOI
10.1073/pnas.89.21.10075
Published
1992-11-01
Pages
10075-8
Language
English
Region
United States
NLM ID
7505876
PMCID
PMC50280
Subset
IM
Grants
NIA NIH HHS · AG-09464 · United States
NIA NIH HHS · AG-10491 · United States
NHLBI NIH HHS · HL-18828 · United States
External Links
PubMed source DOI: 10.1073/pnas.89.21.10075 PMC Full Text View journal details
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