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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.
Erdahl ,
Clifford J.
Chapman ,
Richard W.
Taylor§, and
Douglas R.
Pfeiffer ¶
From the 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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Copyright © 2000 by the American Society for Biochemistry and Molecular Biology.
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