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KCI등재 학술저널

Octyl Gallate Inhibits ATP-induced Intracellular Calcium Increase in PC12 Cells by Inhibiting Multiple Pathways

Octyl Gallate Inhibits ATP-induced Intracellular Calcium Increase in PC12 Cells by Inhibiting Multiple Pathways

Phenolic compounds affect intracellular free Ca<sup>2+</sup> concentration ([Ca<sup>2+</sup>]<sub>i</sub>) signaling. The study examined whether the simple phenolic compound octyl gallate affects ATP-induced Ca<sup>2+</sup> signaling in PC12 cells using fura-2-based digital Ca<sup>2+</sup> imaging and whole-cell patch clamping. Treatment with ATP (100&lt;/SUP&gt;&#1356;M) for 90 s induced increases in [Ca<sup>2+</sup>]<sub>i</sub> in PC12 cells. Pretreatment with octyl gallate (100 nM to 20&#1356;M) for 10 min inhibited the ATP-induced [Ca<sup>2+</sup>]<sub>i</sub> response in a concentration-dependent manner (IC<sub>50</sub>=2.84&#1356;M). Treatment with octyl gallate (3&#1356;M) for 10 min significantly inhibited the ATP-induced response following the removal of extracellular Ca<sup>2+</sup> with nominally Ca<sup>2+</sup>-free HEPES HBSS or depletion of intracellular Ca<sup>2+</sup> stores with thapsigargin (1&#1356;M). Treatment for 10 min with the L-type Ca<sup>2+</sup> channel antagonist nimodipine (1&#1356;M) significantly inhibited the ATP-induced [Ca<sup>2+</sup>]<sub>i</sub> increase, and treatment with octyl gallate further inhibited the ATP-induced response. Treatment with octyl gallate significantly inhibited the [Ca<sup>2+</sup>]<sub>i</sub> 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&#1356;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 [Ca<sup>2+</sup>]<sub>i</sub> increase in PC12 cells by inhibiting both non-selective P2X receptor-mediated influx of Ca<sup>2+</sup> from extracellular space and P2Y receptor-induced release of Ca<sup>2+</sup> from intracellular stores in protein kinase-independent manner. In addition, octyl gallate inhibits the ATP-induced Ca<sup>2+</sup> responses by inhibiting the secondary activation of voltage-gated Ca<sup>2+</sup> channels.

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