Abstract
There is mounting evidence indicating that overexpression or aberrant processing of amyloid precursor protein (βAPP) is causally related to Alzheimer’s disease. βAPP is principally cleaved within the amyloid β protein domain to release a large soluble ectodomain (βAPPs) that has been known to have a wide range of trophic and protective functions. Activation of phospholipase C-coupled receptors has been shown to increase the release of βAPPs through protein kinase C and calcium. Here we have examined whether nicotine can modulate the expression and processing of βAPP in PC12 cells. Treatment of PC12 cells with nicotine increased the release of a carboxyl-terminally truncated, secreted form of βAPP into the conditioned medium without affecting the expression level of βAPP mRNA. The effect of nicotine on the secretion of βAPPs is concentration (>50 μm)- and time (>2 hr)-dependent and attenuated by cotreatment with either mecamylamine, a specific nicotinic receptor antagonist, or EGTA, a calcium chelator, indicating calcium entry through the neuronal nicotinic acetylcholine receptor is essential in enhanced βAPPs release by nicotine. However, nicotine did not significantly change the amyloid β protein secretion from Swedish mutant βAPP-transfected PC12 cells. These results imply that nicotinic receptor agonist might be beneficial in the treatment of Alzheimer’s disease by not only supplementing the deficient cholinergic neurotransmission but also stimulating the release of βAPPs.
Footnotes
- Received November 15, 1996.
- Accepted May 27, 1997.
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Send reprint requests to: Prof. Yoo-Hun Suh, Department of Pharmacology, College of Medicine, Seoul National University, 28 Yongon-dong, Chongno-gu, Seoul, 110–799 Korea. E-mail:yhsuh{at}plaza.snu.ac.kr
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This study was supported by grants-in-aid from Korea Ginseng and Tobacco Research Institute (1994–1996) and Seoul National University Hospital (1997).
- The American Society for Pharmacology and Experimental Therapeutics
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