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Capacitative Ca2+ entry is involved in regulating soluble amyloid precursor protein (sAPPα) release mediated by muscarinic acetylcholine receptor activation in neuroblastoma SH-SY5Y cells
- Title
- Capacitative Ca2+ entry is involved in regulating soluble amyloid precursor protein (sAPPα) release mediated by muscarinic acetylcholine receptor activation in neuroblastoma SH-SY5Y cells
- Authors
- Kim J.H.; Choi S.; Jung J.-E.; Roh E.-J.; Kim H.-J.
- Ewha Authors
- 김화정; 최신규
- SCOPUS Author ID
- 김화정
- Issue Date
- 2006
- Journal Title
- Journal of Neurochemistry
- ISSN
- 0022-3042
- Citation
- Journal of Neurochemistry vol. 97, no. 1, pp. 245 - 254
- Indexed
- SCI; SCIE; SCOPUS
- Document Type
- Article
- Abstract
- Previous studies have demonstrated that stimulation of phospholipase C-linked G-protein-coupled receptors, including muscarinic M1 and M3 receptors, increases the release of the soluble form of amyloid precursor protein (sAPPα) by α-secretase cleavage. In this study, we examined the involvement of capacitative Ca2+ entry (CCE) in the regulation of muscarinic acetylcholine receptor (mAChR)-dependent sAPPα release in neuroblastoma SH-SY5Y cells expressing abundant M3 mAChRs. The sAPPα release stimulated by mAChR activation was abolished by EGTA, an extracellular Ca2+ chelator, which abolished mAChR-mediated Ca 2+ influx without affecting Ca2+ mobilization from intracellular stores. However, mAChR-mediated sAPPα release was not inhibited by thapsigargin, which increases basal [Ca2+]i by depletion of Ca2+ from intracellular stores. While these results indicate that the mAChR-mediated increase in sAPPα release is regulated largely by Ca2+ influx rather than by Ca2+ mobilization from intracellular stores, we further investigated the Ca2+ entry mechanisms regulating this phenomenon. CCE inhibitors such as Gd3+, SKF96365, and 2-aminoethoxydiphenyl borane (2-APB), dose dependently reduced both Ca2+ influx and sAPPα release stimulated by mAChR activation, whereas inhibition of voltage-dependent Ca2+ channels, Na+/Ca2+ exchangers, or Na+-pumps was without effect. These results indicate that CCE plays an important role in the mAChR-mediated release of sAPPα. © 2006 The Authors.
- DOI
- 10.1111/j.1471-4159.2006.03734.x
- Appears in Collections:
- 약학대학 > 약학과 > Journal papers
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