RT Journal Article SR Electronic T1 Enhanced Release of Secreted Form of Alzheimer’s Amyloid Precursor Protein from PC12 Cells by Nicotine JF Molecular Pharmacology JO Mol Pharmacol FD American Society for Pharmacology and Experimental Therapeutics SP 430 OP 436 DO 10.1124/mol.52.3.430 VO 52 IS 3 A1 Seong-Hun Kim A1 Young-Kyung Kim A1 Sung-Jin Jeong A1 Christian Haass A1 Young-Hoon Kim A1 Yoo-Hun Suh YR 1997 UL http://molpharm.aspetjournals.org/content/52/3/430.abstract AB 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.