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J Biol Chem, Vol. 275, Issue 10, 7071-7079, March 10, 2000

Ionomycin, a Carboxylic Acid Ionophore, Transports Pb2+ with High Selectivity*

Warren L. ErdahlDagger , Clifford J. ChapmanDagger , Richard W. Taylor§, and Douglas R. PfeifferDagger

From the Dagger  Department of Medical Biochemistry, Ohio State University, Columbus, Ohio 43210 and the § Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma 73019

Studies utilizing phospholipid vesicle loaded with chelator/indicators for polyvalent cations show that ionomycin transports divalent cations with the selectivity sequence Pb2+ > Cd2+ > Zn2+ > Mn2+ > Ca2+ > Cu2+ > Co2+ > Ni2+ > Sr2+. The selectivity of this ionophore for Pb2+ is in contrast to that observed for A23178 and 4-BrA23187, which transport Pb2+ at efficiencies that are intermediate between those of other cations. When the selectivity difference of ionomycin for Pb2+ versus Ca2+ was calculated from relative rates of transport, with either cation present individually and all other conditions held constant, a value of ~450 was obtained. This rose to ~3200 when both cations were present and transported simultaneously. 1 µM Pb2+ inhibited the transport of 1 mM Ca2+ by ~50%, whereas the rate of Pb2+ transport approached a maximum at a concentration of 10 µM Pb2+ when 1 mM Ca2+ was also present. Plots of log rate versus log ionomycin or log Pb2+ concentration indicated that the transporting species is of 1:1 stoichiometry, ionophore to Pb2+, but that complexes containing an additional Pb2+ may occur. The species transporting Pb2+ may include H·IPb·OH, wherein ionomycin is ionized once and the presence of OH- maintains charge neutrality. Ionomycin retained a high efficiency for Pb2+ transport in A20 B lymphoma cells loaded with Indo-1. Both Pb2+ entry and efflux were observed. Ionomycin should be considered primarily as an ionophore for Pb2+, rather than Ca2+, of possible value for the investigation and treatment of Pb2+ intoxication.


* This work was supported by United States Public Health Service Grant HL49181 from NHLBI, National Institutes of Health, and by the Wallace Research Foundation.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

To whom correspondence should be addressed: Dept. of Medical Biochemistry, Ohio State University, 1645 Neil Ave., 310A Hamilton Hall, Columbus, OH 43210-1218. Tel.: 614-292-8774; Fax: 614-292-4118.


Copyright © 2000 by The American Society for Biochemistry and Molecular Biology, Inc.
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