La ³⁺ Inhibits the UTP-induced Ca ²⁺ Mobilization in MDCK Cells

We have studied the effects of La ³⁺ on UTP-induced rises in intracellular calcium levels ([Ca ²⁺ ] _i ) measured by fura-2 fluorimetry in Madin Darby canine kidney (MDCK) cells. UTP induced [Ca ²⁺ ] _i rises dose-dependently with an EC ₅₀ of 1 mM. The Ca ²⁺ signal was triggered by a Ca ²⁺ release from the inositol 1,4,5-trisphosphate (IP ₃ )-sensitive pool because the signal was completely blocked by pretreatment of the endoplasmic reticulum (ER) Ca ²⁺ pump inhibitor thapsigargin (TG) or the phospholipase C (PLC) inhibitor U73122. Both the peak height and under-curve area of 10 μM UTP-induced Ca ²⁺ signal was reduced by approximately 40% by extracellular Ca ²⁺ removal, suggesting that UTP induced capacitative Ca ²⁺ entry. La ³⁺ inhibited the UTP-induced Ca ²⁺ signal dose-dependently when added before or after UTP. Pretreatment of 0.1 mM La ³⁺ inhibited the UTP response more than Ca ²⁺ removal did. The mechanisms underlying the La ³⁺ inhibition appear to involve not only block of capacitative Ca ²⁺ entry.