Capacitative Ca2+ entry is involved in regulating soluble amyloid precursor protein (sAPPα) release mediated by muscarinic acetylcholine receptor activation in neuroblastoma SH-SY5Y cells

被引:16
|
作者
Kim, JH [1 ]
Choi, S [1 ]
Jung, JE [1 ]
Roh, EJ [1 ]
Kim, HJ [1 ]
机构
[1] Ewha Womans Univ, Coll Pharm, Pharmaceut Sci Res Inst, Seoul 120750, South Korea
关键词
alpha-secretase; capacitative Ca2+ entry; G-protein coupled receptors; intracellular Ca2+ response; store-operated Ca2+ channel;
D O I
10.1111/j.1471-4159.2006.03734.x
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Previous studies have demonstrated that stimulation of phospholipase C-linked G-protein-coupled receptors, including muscarinic M-1 and M-3 receptors, increases the release of the soluble form of amyloid precursor protein (sAPP alpha) by alpha-secretase cleavage. In this study, we examined the involvement of capacitative Ca2+ entry (CCE) in the regulation of muscarinic acetylcholine receptor (mAChR)-dependent sAPP alpha release in neuroblastoma SH-SY5Y cells expressing abundant M3 mAChRs. The sAPP alpha release stimulated by mAChR activation was abolished by EGTA, an extracellular Ca2+ chelator, which abolished mAChR-mediated Ca2+ influx without affecting Ca2+ mobilization from intracellular stores. However, mAChR-mediated sAPP alpha 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 sAPP alpha 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 sAPP alpha 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 sAPP alpha.
引用
收藏
页码:245 / 254
页数:10
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