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
- Yujie Guo Yi Jae Hong Hyun-Jong Jang Myung-Jun Kim Duck-Joo Rhie Yang-Hyeok Jo Sang June Hahn Shin H
- 대한생리학회-대한약리학회
- The Korean Journal of Physiology & Pharmacology
- 제14권 제1호
- 등재여부 : KCI등재
- 2010.01
- 21 - 28 (8 pages)
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</SUP>ՌM) for 90 s induced increases in [Ca<sup>2+</sup>]<sub>i</sub> in PC12 cells. Pretreatment with octyl gallate (100 nM to 20ՌM) for 10 min inhibited the ATP-induced [Ca<sup>2+</sup>]<sub>i</sub> response in a concentration-dependent manner (IC<sub>50</sub>=2.84ՌM). Treatment with octyl gallate (3ՌM) 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 (1ՌM). Treatment for 10 min with the L-type Ca<sup>2+</sup> channel antagonist nimodipine (1ՌM) 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 (50ՌM) 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.