Effect of tetramethylpyrazine (TMP) on Ca 2+ signal transduction and cell viability in a model of renal tubular cells

Tetramethylpyrazine (TMP) is a compound purified from herb. Its effect on Ca 2+ concentrations ([Ca 2+ ] i ) in renal cells is unclear. This study examined whether TMP altered Ca 2+ signaling in Madin‐Darby canine kidney (MDCK) cells. TMP at 100–800 μM induced [Ca 2+ ] i rises, which were reduced by Ca 2+ removal. TMP induced Mn 2+ influx implicating Ca 2+ entry. TMP‐induced Ca 2+ entry was inhibited by 30% by modulators of protein kinase C (PKC) and store‐operated Ca 2+ channels. Treatment with the endoplasmic reticulum Ca 2+ pump inhibitor 2,5‐di‐tert‐butylhydroquinone (BHQ) inhibited 93% of TMP‐evoked [Ca 2+ ] i rises. Treatment with TMP abolished BHQ‐evoked [Ca 2+ ] 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 Ca 2+  chelator 1,2‐bis(2‐aminophenoxy)ethane‐N,N,N′,N′‐tetraacetic acid‐acetoxymethyl ester. Together, in MDCK cells, TMP induced [Ca 2+ ] i rises by evoking PLC‐dependent Ca 2+ release from endoplasmic reticulum and Ca 2+ entry via PKC‐sensitive store‐operated Ca 2+ entry. TMP also caused Ca 2+ ‐independent cell death.