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Capacitative Ca 2+ entry is involved in regulating soluble amyloid precursor protein (sAPPα) release mediated by muscarinic acetylcholine receptor activation in neuroblastoma SH‐SY5Y cells
Author(s) -
Kim Jin Hyoung,
Choi Sinkyu,
Jung JiEun,
Roh EunJihn,
Kim HwaJung
Publication year - 2006
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/j.1471-4159.2006.03734.x
Subject(s) - muscarinic acetylcholine receptor , thapsigargin , chemistry , sh sy5y , intracellular , muscarinic acetylcholine receptor m3 , extracellular , egta , endocrinology , acetylcholine , muscarinic acetylcholine receptor m1 , phospholipase c , medicine , receptor , microbiology and biotechnology , biochemistry , biology , calcium , cell culture , neuroblastoma , organic chemistry , genetics
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 (sAPPα) by α‐secretase cleavage. In this study, we examined the involvement of capacitative Ca 2+ 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 Ca 2+ chelator, which abolished mAChR‐mediated Ca 2+ influx without affecting Ca 2+ mobilization from intracellular stores. However, mAChR‐mediated sAPPα release was not inhibited by thapsigargin, which increases basal [Ca 2+ ] i by depletion of Ca 2+ from intracellular stores. While these results indicate that the mAChR‐mediated increase in sAPPα release is regulated largely by Ca 2+ influx rather than by Ca 2+ mobilization from intracellular stores, we further investigated the Ca 2+ entry mechanisms regulating this phenomenon. CCE inhibitors such as Gd 3+ , SKF96365, and 2‐aminoethoxydiphenyl borane (2‐APB), dose dependently reduced both Ca 2+ influx and sAPPα release stimulated by mAChR activation, whereas inhibition of voltage‐dependent Ca 2+ channels, Na + /Ca 2+ exchangers, or Na + ‐pumps was without effect. These results indicate that CCE plays an important role in the mAChR‐mediated release of sAPPα.