The ionophore nigericin transports Pb2+ with high activity and selectivity: a comparison to monensin and ionomycin.
The K(+) ionophore nigericin is shown to be highly effective as an ionophore for Pb(2+) but not other divalent cations, including Cu(2+), Zn(2+), Cd(2+), Mn(2+), Co(2+), Ca(2+), Ni(2+), and Sr(2+). Among this group a minor activity for Cu(2+) transport is seen, while for the others activity is near or below the limit of detection. The selectivity of nigericin for Pb(2+) exceeds that of ionomycin or monensin and arises, at least in part, from a high stability of nigericin-Pb(2+) complexes. Plots of log rate vs log Pb(2+) or log ionophore concentration, together with the pH dependency, indicate that nigericin transports Pb(2+) via the species NigPbOH and by a mechanism that is predominately electroneutral. As with monensin and ionomycin, a minor fraction of activity may be electrogenic, based upon a stimulation of rate that is produced by agents which prevent the formation of transmembrane electrical potentials. Nigericin-catalyzed Pb(2+) transport is not inhibited by physiological concentrations of Ca(2+) or Mg(2+) and is only modestly affected by K(+) and Na(+) concentrations in the range of 0-100 mM. These characteristics, together with higher selectivity and efficiency, suggest that nigericin may be more useful than monensin in the treatment of Pb intoxication.
Hamidinia
Shawn A
SA
Department of Molecular and Cellular Biochemistry, The Ohio State University, Columbus, Ohio 43210, USA.
Tan
Bo
B
Erdahl
Warren L
WL
Chapman
Clifford J
CJ
Taylor
Richard W
RW
Pfeiffer
Douglas R
DR
D002413:Cations, Divalent / Q000737:chemistry / Q000378:metabolism; D017136:Ion Transport / Q000187:drug effects; D015759:Ionomycin / Q000737:chemistry; D007476:Ionophores / Q000737:chemistry / Q000378:metabolism*; D007854:Lead / Q000737:chemistry / Q000378:metabolism*; D008081:Liposomes / Q000737:chemistry; D008672:Metals, Alkali / Q000494:pharmacology; D008673:Metals, Alkaline Earth / Q000494:pharmacology; D008985:Monensin / Q000737:chemistry; D009550:Nigericin / Q000737:chemistry / Q000378:metabolism*; D010713:Phosphatidylcholines / Q000737:chemistry
D002413:Cations, Divalent; D007476:Ionophores; D008081:Liposomes; D008672:Metals, Alkali; D008673:Metals, Alkaline Earth; D010713:Phosphatidylcholines; D007854:Lead; D015759:Ionomycin; D008985:Monensin; D009550:Nigericin; C028694:1-palmitoyl-2-oleoylphosphatidylcholine