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dc.titleEffects of celecoxib on voltage-gated calcium channel currents in rat pheochromocytoma (PC12) cells
dc.contributor.authorZhang, Y.
dc.contributor.authorDing, G.
dc.contributor.authorCheng, Y.
dc.contributor.authorSun, W.
dc.contributor.authorTao, J.
dc.contributor.authorHuang, H.
dc.identifier.citationZhang, Y., Ding, G., Cheng, Y., Sun, W., Tao, J., Huang, H. (2007). Effects of celecoxib on voltage-gated calcium channel currents in rat pheochromocytoma (PC12) cells. Pharmacological Research 56 (3) : 267-274. ScholarBank@NUS Repository.
dc.description.abstractCyclooxygenase-2 (COX-2) plays crucial roles in the development and invasion of tumors. Celecoxib, a selective COX-2 inhibitor, has been shown to be chemopreventive against cancer. However, to date, the mechanisms of these effects remain unclear. In this study, we investigate the effects of celecoxib on voltage-gated calcium channel (VGCC) currents in undifferentiated pheochromocytoma (PC12) cells using whole-cell patch clamp. Our results showed that celecoxib, instead of rofecoxib or NS-398, another selective COX-2 inhibitor, reversibly inhibited the current density of VGCC in a concentration-dependent manner, but had no apparent effects on the cells treated with nifedipine (1 μM), an L-type calcium channel blocker. Upon pre-incubation of PC12 cells with omega-conotoxia GVIA (1 μM), an N-type calcium channel blocker, omega-agatoxin IVA (1 μM), a P/Q-type calcium channel blocker, or SNX-482 (1 μM), a R-type calcium channel blocker, celecoxib (1 μM) inhibited the currents by 36%, 28%, and 25%, respectively. Celecoxib up-shifted the current-voltage (I-V), and hyperpolarizedly shifted the inactivation curve, but did not markedly affect the activation curve. Intracellular application of H89, a protein kinase A inhibitor, failed to affect the celecoxib's VGCC currents inhibition. Taken together, our present results suggested that celecoxib inhibited L-type calcium channels in PC12 cells via a COX-2 independent pathway, which might be responsible for its clinical effects including anti-tumor. © 2007.
dc.subjectPC12 cells
dc.subjectVoltage-gated calcium channel (VGCC)
dc.subjectWhole-cell patch clamp
dc.description.sourcetitlePharmacological Research
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