Effect of Protriptyline on [Ca^(2+)]i and Viability in MDCK Renal Tubular Cells

He-Hsiung Cheng ； Chiang-Ting Chou ； Wei-Zhe Liang ； Chun-Chi Kuo ； Pochuen Shieh ； Jue-Long Wang ； Chung-Ren Jan

《The Chinese Journal of Physiology》 60卷2期 (2017/04) Pp. 114-123

https://doi.org/10.4077/CJP.2017.BAF459

摘要

Protriptyline has been used as an antidepressant. Clinically it has been prescribed in the auxiliary treatment of cancer patients. However, its effect on Ca^(2+) signaling and related physiology is unknown in renal cells. This study examined the effect of protriptyline on cytosolic free Ca^(2+) concentrations ([Ca^(2+)]i) and viability in Madin-Darby canine kidney (MDCK) tubular cells. Protriptyline induced [Ca^(2+)]i rises concentration-dependently. The response was reduced by 20% by removing extracellular Ca^(2+). Protriptyline-induced Ca^(2+) entry was not altered by protein kinase C (PKC) activity but was inhibited by 20% by three modulators of store-operated Ca^(2+) channels: nifedipine, econazole and SKF96365. In Ca^(2+)-free medium, treatment with the endoplasmic reticulum Ca^(2+) pump inhibitor 2,5- di-tert-butylhydroquinone (BHQ) or thapsigargin partially inhibited protriptyline-evoked [Ca^(2+)]i rises. Conversely, treatment with protriptyline inhibited partially BHQ or thapsigargin-evoked [Ca^(2+)]i rises. Inhibition of phospholipase C (PLC) with U73122 did not change protriptyline-induced [Ca^(2+)]i rises. Protriptyline at 5-200 μM decreased cell 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 (BAPTA/ AM). Together, in MDCK cells, protriptyline induced [Ca^(2+)]i rises by evoking PLC-independent Ca^(2+) release from the endoplasmic reticulum and other unknown stores, and Ca^(2+) entry via PKC-insensitive store-operated Ca^(2+) entry. Protriptyline also caused Ca^(2+)-independent cell death.

關鍵字

Ca^(2+) ； MDCK cells ； protriptyline ； renal tubular cells

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