Surface binding and uptake of nickel(II) in human epithelial kidney cells: modulation by ionomycin, nicardipine and metals.
The carcinogenic potency of nickel compounds depends on the ability of nickel ions to enter target cells. The presumptive preventive potential of several metals against nickel-induced cancer may depend on their capacity to inhibit nickel uptake. Surface binding and uptake of 63Ni2+ in immortalized human kidney epithelial (IHKE) cells suspended in a salts/glucose minimal medium was studied at 0.085 mM nickel. Nickel uptake, after a rapid phase of about 2 h, continued at a slower rate for several hours. Nicardipine (50 microM) decreased uptake to about 25% of control values. Ionomycin (3 microM) increased uptake 4- to 5-fold. Nickel uptake into IHKE cells was decreased by metal cations. In the absence of ionomycin, this effect followed the order Zn > Cd > Co > Mn > Mg >> Ca. In the presence of ionomycin the order was Zn > Cd > Co > Mn >> Ca > Mg. These metals inhibited uptake more strongly than binding to the cell surface. However, Co2+ reduced surface binding strongly in ionomycin-potentiated uptake. With no ionomycin present, 0.15 mM Zn2+, 1 mM Mn2+, 4 mM Mg2+ or 70 mM Ca2+ caused 80-85% inhibition of nickel uptake. In the absence of ionomycin, calcium was a weaker inhibitor of nickel uptake than magnesium. In the presence of ionomycin, calcium was a stronger inhibitor than magnesium. The results indicate that nickel can be taken up through calcium channels in IHKE cells. It is suggested that ionomycin-potentiated transport mechanisms, under the conditions applied, are different from normal mechanisms of transport functioning in the absence of ionomycin. Different metals, essential and non-essential, seem to be inhibitors or competitors for the transport mechanisms.
Refsvik
T
T
Department of Toxicology, National Institute of Occutional Health, Oslo, Norway.
Andreassen
T
T
D001692:Biological Transport / Q000187:drug effects; D002413:Cations, Divalent / Q000494:pharmacology; D002461:Cell Line, Transformed; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D004848:Epithelium / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology*; D007668:Kidney / Q000378:metabolism*; D007700:Kinetics; D008670:Metals / Q000494:pharmacology*; D009529:Nicardipine / Q000494:pharmacology*; D009532:Nickel / Q000378:metabolism*
D002413:Cations, Divalent; D008670:Metals; D015759:Ionomycin; D009532:Nickel; D009529:Nicardipine