La3+ inhibits the UTP-induced Ca2+ mobilization in MDCK cells

We have studied the effects of La3+ on UTP-induced rises in intracellular calcium levels ([Ca2+]i) measured by fura-2 fluorimetry in Madin Darby canine kidney (MDCK) cells. UTP induced [Ca2+]i rises dose-dependently with an EC50 of 1 mM. The Ca2+ signal was triggered by a Ca2+ release from the inositol 1,4,5-trisphosphate (IP3)-sensitive pool because the signal was completely blocked by pretreatment of the endoplasmic reticulum (ER) Ca2+ pump inhibitor thapsigargin (TG) or the phospholipase C (PLC) inhibitor U73,122. Both the peak height and under-curve area of 10 microM UTP-induced Ca2+ signal was reduced by approximately 40% by extracellular Ca2+ removal, suggesting that UTP induced capacitative Ca2+ entry. La3+ inhibited the UTP-induced Ca2+ signal dose-dependently when added before or after UTP. Pretreatment of 0.1 mM La3+ inhibited the UTP response more than Ca2+ removal did. The mechanisms underlying the La3+ inhibition appear to involve not only block of capacitative Ca2+ entry.