title: Surface binding and uptake of nickel(II) in human epithelial kidney cells: modulation by ionomycin, nicardipine and metals.
abstract: 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.
authors.affiliation: Department of Toxicology, National Institute of Occutional Health, Oslo, Norway.
authors.forename: T
authors.initials: T
authors.lastname: Refsvik
authors.forename: T
authors.initials: T
authors.lastname: Andreassen
mesh_terms: 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*
chemical_list: D002413:Cations, Divalent; D008670:Metals; D015759:Ionomycin; D009532:Nickel; D009529:Nicardipine