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Effect of capsazepine on [Ca 2+ ] i in MDCK renal tubular cells
Author(s) -
Tsai JengYu,
Kuo ChunChi,
Chou ChiangTing,
Chao David,
Cheng HeHsiung,
Wang JueLong,
Cheng JinShiung,
Lin KoLong,
Huang JongKhing,
Chang HongTai,
Jan ChungRen
Publication year - 2011
Publication title -
drug development research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.582
H-Index - 60
eISSN - 1098-2299
pISSN - 0272-4391
DOI - 10.1002/ddr.20433
Subject(s) - capsazepine , thapsigargin , ionomycin , chemistry , endoplasmic reticulum , phospholipase c , biophysics , fura 2 , protein kinase c , biochemistry , intracellular , cytosol , trpv1 , biology , signal transduction , receptor , transient receptor potential channel , enzyme
The current study explored whether capsazepine changed basal cytosolic free Ca 2+ concentrations ([Ca 2+ ] i ) levels in suspended Madin Darby canine kidney (MDCK) cells cells by using fura‐2 as a Ca 2+ ‐selective fluorescent dye. At concentrations of 10–200 µM, capsazepine increased [Ca 2+ ] i in a concentration‐dependent manner. The Ca 2+ signal was partially reduced by 40% by removing extracellular Ca 2+ . Capsazepine induced Mn 2+ quench of fura‐2 fluorescence, indirectly implicating Ca 2+ entry. Capsazepine‐induced Ca 2+ influx was unchanged by L‐type Ca 2+ entry inhibitors and protein kinase C modulators [phorbol 12‐myristate 13‐acetate (PMA) and GF109203X]. In Ca 2+ ‐free medium, 100 µM capsazepine‐induced Ca 2+ release was substantially suppressed by pretreatment with thapsigargin (an endoplasmic reticulum Ca 2+ pump inhibitor). Pretreatment with capsazepine nearly abolished thapsigargin‐induced Ca 2+ release. Inhibition of phospholipase C with U73122 did not change capsazepine‐induced [Ca 2+ ] i rises. Collectively, in MDCK cells, capsazepine induced [Ca 2+ ] i rises by causing phospholipase C‐independent Ca 2+ release from the endoplasmic reticulum and Ca 2+ influx via non‐L‐type Ca 2+ channels. Drug Dev Res 72: 323–329, 2011. © 2010 Wiley‐Liss, Inc.