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

Abstract

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.

Research progress of aconitine toxicity and forensic analysis of aconitine poisoning

“…Ca 2þ is one of the important second messengers and plays crucial roles in the process of cells signal transduction and electrical activity of myocardial cells [54][55][56][57]. Meanwhile, disruption of the intracellular Ca 2þ homeostasis is an important mechanism of arrhythmic toxicity of aconitine [51].…”