Effect of Celecoxib on Ca2+ Fluxes and Proliferation in MDCK Renal Tubular Cells

Abstract

The effect of celecoxib on renal tubular cells is largely unexplored. In Madin Darby canine kidney (MDCK) cells, the effect of celecoxib on intracellular Ca2 + concentration ([Ca2 +]i) and proliferation was examined by using the Ca2 +-sensitive fluorescent dye fura-2 and the viability detecting fluorescent dye tetrazolium, respectively. Celecoxib (≥1 μ M) caused an increase of [Ca2 +]i in a concentration-dependent manner. Celecoxib-induced [Ca2 +]i increase was partly reduced by removal of extracellular Ca2 +. Celecoxib-induced Ca2 + influx was independently suggested by Mn2 + influx-induced fura-2 fluorescence quench. In Ca2 +-free medium, thapsigargin, an inhibitor of the endoplasmic reticulum Ca2 +-ATPase, caused a monophasic [Ca2 +]i increase, after which celecoxib only induced a tiny [Ca2 +]iincrease; conversely, pretreatment with celecoxib completely inhibited thapsigargin-induced [Ca2 +]i increases. U73122, an inhibitor of phospholipase C, abolished ATP (but not celecoxib)-induced [Ca2 +]i increases. Overnight incubation with 1 or 10 μ M celecoxib decreased cell viability by 80% and 100%, respectively. These data indicate that celecoxib evokes a [Ca2 +]i increase in renal tubular cells by stimulating both extracellular Ca2 + influx and intracellular Ca2 + release and is highly toxic to renal tubular cells in vitro.