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KMID : 0811720100140010021
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Korean Journal of Physiology & Pharmacology
2010 Volume.14 No. 1 p.21 ~ p.28
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Octyl Gallate Inhibits ATP-induced Intracellular Calcium Increase in PC12 Cells by Inhibiting Multiple Pathways
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Guo Yu-Jie
Hong Yi-Jae
Jang Hyun-Jong
Kim Myung-Jun
Rhie Duck-Joo
Jo Yang-Hyeok
Hahn Sang-June
Yoon Shin-Hee
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Abstract
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Phenolic compounds affect intracellular free Ca2＋ concentration ([Ca2＋]i) signaling. The study examined whether the simple phenolic compound octyl gallate affects ATP-induced Ca2＋ signaling in PC12 cells using fura-2-based digital Ca2＋ imaging and whole-cell patch clamping. Treatment with ATP (100?M) for 90 s induced increases in [Ca2＋]i in PC12 cells. Pretreatment with octyl gallate (100 nM to 20?M) for 10 min inhibited the ATP-induced [Ca2＋]i response in a concentration-dependent manner (IC50=2.84?M). Treatment with octyl gallate (3?M) for 10 min significantly inhibited the ATP-induced response following the removal of extracellular Ca2＋ with nominally Ca2＋-free HEPES HBSS or depletion of intracellular Ca2＋ stores with thapsigargin (1?M). Treatment for 10 min with the L-type Ca2＋ channel antagonist nimodipine (1?M) significantly inhibited the ATP-induced [Ca2＋]i increase, and treatment with octyl gallate further inhibited the ATP-induced response. Treatment with octyl gallate significantly inhibited the [Ca2＋]i increase induced by 50 mM KCl. Pretreatment with protein kinase C inhibitors staurosporin (100 nM) and GF109203X (300 nM), or the tyrosine kinase inhibitor genistein (50?M) did not significantly affect the inhibitory effects of octyl gallate on the ATP-induced response. Treatment with octyl gallate markedly inhibited the ATP-induced currents. Therefore, we conclude that octyl gallate inhibits ATP-induced [Ca2＋]i increase in PC12 cells by inhibiting both non-selective P2X receptor-mediated influx of Ca2＋ from extracellular space and P2Y receptor-induced release of Ca2＋ from intracellular stores in protein kinase-independent manner. In addition, octyl gallate inhibits the ATP-induced Ca2＋ responses by inhibiting the secondary activation of voltage-gated Ca2＋ channels.
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KEYWORD
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Ca2＋, Flavonoid, Octyl gallate, PC12 cells, Phenolic compound, Purinergic receptor, Voltage-gated Ca2＋ channels
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