The cholinergic agonist carbachol reduces intracellular beta-amyloid precursor protein in PC 12 and C6 cells.
Amyloid beta-protein, the major constituent of amyloid plaques in Alzheimer's disease, is derived from larger amyloid precursor proteins (APP). Changes in the rates and or pathways of APP synthesis and degradation may be central to the deposition of beta-amyloid. We explored the possibility that APP processing is regulated by activation of endogenous cell-surface neurotransmitter receptors by stimulating C6, PC12 and neuroblastoma cells with the cholinergic agonist carbachol. We measured the intracellular APP in these cell lines by western blotting using three antibodies against different regions of APP. When cells were treated with carbachol for different periods, PC12 and C6 cells responded with a sharp decrease of APP bands. Similar blots probed with an antibody against heat-shock protein (HSP), showed no change in the intensity of the immunoreactive HSP-70 band. These results suggest that the decrease in intracellular APP seen after stimulation by carbachol has some specificity and that APP processing may be regulated by stimulation of cholinergic receptors on the surface of cells.
Lahiri
D K
DK
Department of Psychiatry, Indiana University School of Medicine, Indianapolis 46202.
Nall
C
C
Farlow
M R
MR
D016564:Amyloid beta-Protein Precursor / Q000737:chemistry / Q000378:metabolism*; D000818:Animals; D015153:Blotting, Western; D002217:Carbachol / Q000494:pharmacology*; D006360:Heat-Shock Proteins / Q000378:metabolism; D009447:Neuroblastoma; D016716:PC12 Cells; D051381:Rats; D011950:Receptors, Cholinergic / Q000378:metabolism*; D014407:Tumor Cells, Cultured
D016564:Amyloid beta-Protein Precursor; D006360:Heat-Shock Proteins; D011950:Receptors, Cholinergic; D002217:Carbachol