Effects of the Chinese herb component phellopterin on the increase in cytosolic free calcium in PC12 cells

Autor: Jia-Bin Qiu, Hai-Tao Li, Ling He
Rok vydání: 2007
Předmět:
Zdroj: Drug Development Research. 68:79-83
ISSN: 1098-2299
0272-4391
Popis: The present study investigated the effects of the Chinese Herb component, phellopterin on high K+ and glutamate-induced extracellular calcium influx and caffeine or cyclopiazonic acid (CPA)-induced calcium release from internal stores in attached PC12 cells. Attached cells were loaded with the calcium fluorescent indicator Fluo-3/AM with the final concentration of 5 µM for 50 min at 37°C and cytosolic free Ca2+ measured as fluorescent intensity (FI) (excitation: 488 nm; emission: 535 nm). When PC12 cells were exposed to extracellular Ca2+([Ca2+]0) 2.0 mM, the FI for resting [Ca2+]i was 1,188±163, high K+ (75 mM) and glutamate (10 mM) induced an increase in [Ca2+]i with peak values of 4,270±982 and 3,096±402, respectively. Phellopterin (0.1–100 µM) had no apparent effect on resting [Ca2+]i, but inhibited high K+ and glutamate induced the increase in [Ca2+]i in a dose-dependent manner. When PC12 cells were exposed to Ca2+-free solution, the FI for resting [Ca2+]i was 804±77. Caffeine (40 mM) and CPA (30 µM) stimulated Ca2+ release from caffeine-ryanodine and inositol 1,4,5-tris-phosphate (InsP3)-sensitive internal calcium stores, inducing an increase in [Ca2+]i to 2,938±362 and 1,816±291, respectively. Phellopterin (0.1–100 µmol/L) inhibited caffeine and CPA stimulated intracellular calcium release in a dose-dependent manner. In summary, phellopterin, a novel component isolated from Changii radix, inhibited Ca2+ influx induced by stimulation of voltage-gated and receptor-dependent calcium channels with a greater inhibition of receptor-dependent calcium channels. It also inhibited Ca2+ release from caffeine-ryanodine and InsP3-sensitive internal stores, being more potent for caffeine stimulation. Phellopterin may be a promising candidate for the development of new classes of calcium antagonists. Drug Dev Res 68:79–83, 2007. © 2007 Wiley-Liss, Inc.
Databáze: OpenAIRE
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