Effect of triethyltin on Ca2+ movement in Madin–Darby canine kidney cells

The effects of the environmental toxicant, triethyltin, on Ca² + mobilization in Madin–Darby canine kidney (MDCK) cells have been examined. Triethyltin induced an increase in cytosolic free Ca² + levels ([Ca² +]_i) at concentrations larger than 2 mM in a concentrationdependent manner. Within 5 min, the [Ca² +]_i signal was composed of a gradual rise and a sustained phase. The [Ca² +]_i signal was partly reduced by removing extracellular Ca² +. In Ca² +-free medium, pretreatment with thapsigargin (1 mM), an endoplasmic reticulum Ca² + pump inhibitor, reduced 50 mM triethyltin-induced [Ca² +]_i increase by 80%. Conversely, pretreatment with triethyltin abolished thapsigargin-induced Ca² + release. Pretreatment with U73122 (2 mM) to inhibit phospholipase C-coupled inositol 1,4,5-trisphosphate formations failed to alter 50 mM triethyltin-induced Ca² + release. Incubation with triethyltin at a concentration (1 mM) that did not increase basal [Ca² +]_i for 3 min did not alter ATP (10 mM)and bradykinin (1 mM)-induced [Ca² +]_i increases. Collectively, this study shows that triethyltin altered Ca² + movement in renal tubular cells by releasing Ca² + from multiple stores in an inositol 1,4,5-trisphosphate-independent manner, and by inducing Ca² + influx.