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J. Biol. Chem., Vol. 277, Issue 41, 38111-38120, October 11, 2002

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Monensin Mediates a Rapid and Selective Transport of Pb²⁺
POSSIBLE APPLICATION OF MONENSIN FOR THE TREATMENT OF Pb²⁺ INTOXICATION^*

Shawn A. Hamidinia, Olga I. Shimelis^§, Bo Tan^§, Warren L. Erdahl, Clifford J. Chapman, Gordon D. Renkes^¶, Richard W. Taylor^§, and Douglas R. Pfeiffer

From the  Departments of Molecular and Cellular Biochemistry and the ^¶ Department of Chemistry, Ohio State University, Columbus, Ohio 43210 and the ^§ Department of Chemistry and Biochemistry, University of Oklahoma, Norman, Oklahoma 73019

The carboxylic acid ionophore monensin, known as an electroneutral Na⁺ ionophore, an anticoccidial agent, and a growth-promoting feed additive in agriculture, is shown to be highly efficient as an ionophore for Pb²⁺ and to be highly selective for Pb²⁺ compared with other divalent cations. Monensin transports Pb²⁺ by an electroneutral mechanism in which the complex PbMonOH is the transporting species. Electrogenic transport via the species PbMon⁺ may also be possible. Monensin catalyzed Pb²⁺ transport is little affected by Ca²⁺, Mg²⁺, or K⁺ concentrations that are encountered in living systems. Na⁺ is inhibitory, but its effectiveness at 100 mM does not exceed ~50%. The poor activity of monensin as an ionophore for divalent cations other than Pb²⁺ is consistent with the pattern of complex formation constants observed in the mixed solvent 80% methanol/water. This pattern also explains why Ca²⁺, Mg²⁺, and K⁺ are ineffective as inhibitors of Pb²⁺ transport, but it does not fully explain the actions of Na⁺, where kinetic features of the transport mechanism may also be important. When given to rats at 100 ppm in feed together with Pb²⁺ at 100 ppm in drinking water, monensin reduces Pb accumulation in several organs and tissues. It also accelerates the excretion of Pb that was accumulated previously and produces this effect without depleting the organs of zinc or copper. Monensin, used alone or in combination with other agents, may be useful for the treatment of Pb intoxication.

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