Effect of triethyltin on Ca ²⁺ movement in Madin-Darby canine kidney cells

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