Effect of capsaicin on Ca2+ fluxes in Madin-Darby canine renal tubular cells

Jeng Hsien Yeh, Jenn Kuen Lee, Jyh Seng Wang, Mei Yin Yeh, Yu Lin Yang, Jau Shyang Huang, Wen Teng Chang, Daih Huang Kuo, Pochuen Shieh, Fu An Chen, Chun Chi Kuo, Chung Ren Jan*

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

1 Scopus citations

Abstract

(Table Presented) The effect of capsaicin, a transient receptor potential vanniloid-1 (TRPV1) receptor agonist, on cytosolic free Ca2+ concentrations ([Ca2+]i) in Madin Darby canine kidney (MDCK) cells is unclear. This study explored whether capsaicin changed basal [Ca2+]i levels in suspended MDCK cells by using fura-2 as a Ca2+-sensitive fluorescent dye. Capsaicin at concentrations between 10-100 μM increased [Ca2+]i in a concentration- dependent manner. The Ca2+ signal was reduced by 80% by removing extracellular Ca2+. Capsacin induced Mn2+ influx, leading to quench of fura-2 fluorescence suggesting Ca2+ influx. This Ca 2+ influx was inhibited by phospholipase A2 inhibitor aristolochic acid and the non-selective Ca2+ entry blocker La3+, but not by store-operated Ca2+ channel blockers nifedipine, econazole, and SK&F96365, and protein kinase C/A modulators. In Ca2+-free medium, pretreatment with the endoplasmic reticulum Ca2+ pump inhibitor thapsigargin abolished capsaicin-induced Ca2+ release. Conversely, pretreatment with capsaicin partly reduced thapsigargin-induced [Ca2+]i rise. Inhibition of phospholipase C with U73122 did not alter capsaicin-induced [Ca2+]i rise. The TRPV1 receptor antagonist capsazepine also induced significant Ca2+ entry and Ca2+ release. Collectively, in MDCK cells, capsaicin induced [Ca2+]i rises by causing phospholipase C-independent Ca2+ release from the endoplasmic reticulum and Ca2+ influx via phospholipase A2-regulated, La3+-sensitive Ca2+ channels in a manner dissociated from stimulation of TRPV1 receptors.

Original languageEnglish
Pages (from-to)112-119
Number of pages8
JournalDrug Development Research
Volume71
Issue number2
DOIs
StatePublished - 04 2010
Externally publishedYes

Keywords

  • Ca
  • Capsaicin
  • MDCK
  • Renal cells

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