Effect of tetramethylpyrazine (TMP) on Ca2+ signal transduction and cell viability in a model of renal tubular cells

Yi Chien Fang, Chiang Ting Chou, Wei Zhe Liang, Chun Chi Kuo, Shu Shong Hsu*, Jue Long Wang, Chung Ren Jan

*Corresponding author for this work

Research output: Contribution to journalJournal Article peer-review

1 Scopus citations


Tetramethylpyrazine (TMP) is a compound purified from herb. Its effect on Ca2+ concentrations ([Ca2+]i) in renal cells is unclear. This study examined whether TMP altered Ca2+ signaling in Madin-Darby canine kidney (MDCK) cells. TMP at 100–800 μM induced [Ca2+]i rises, which were reduced by Ca2+ removal. TMP induced Mn2+ influx implicating Ca2+ entry. TMP-induced Ca2+ entry was inhibited by 30% by modulators of protein kinase C (PKC) and store-operated Ca2+ channels. Treatment with the endoplasmic reticulum Ca2+ pump inhibitor 2,5-di-tert-butylhydroquinone (BHQ) inhibited 93% of TMP-evoked [Ca2+]i rises. Treatment with TMP abolished BHQ-evoked [Ca2+]i rises. Inhibition of phospholipase C (PLC) abolished TMP-induced responses. TMP at 200–1000 μM decreased viability, which was not reversed by pretreatment with the Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N′,N′-tetraacetic acid-acetoxymethyl ester. Together, in MDCK cells, TMP induced [Ca2+]i rises by evoking PLC-dependent Ca2+ release from endoplasmic reticulum and Ca2+ entry via PKC-sensitive store-operated Ca2+ entry. TMP also caused Ca2+-independent cell death.

Original languageEnglish
Article numbere21952
JournalJournal of Biochemical and Molecular Toxicology
Issue number10
StatePublished - 10 2017
Externally publishedYes

Bibliographical note

Publisher Copyright:
© 2017 Wiley Periodicals, Inc.


  • Ca2+
  • Cytotoxicity
  • Renal tubular cells
  • Tetramethylpyrazine


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