Monensin Mediates a Rapid and Selective Transport of Pb super(2+). Possible application of monensin for the treatment of Pb super(2+) intoxication

• Published in: The Journal of biological chemistry 2002-10, Vol.277 (41), p.38111-38120
• Main Authors: Hamidinia, SA, Shimelis, OI, Tan, B, Erdahl, W L, Chapman, C J, Renkes, G D, Taylor, R W, Pfeiffer, DR
• Format: Article
• Language: English
• ISSN: 0021-9258

The carboxylic acid ionophore monensin, known as an electroneutral Na super(+) ionophore, an anticoccidial agent, and a growth-promoting feed additive in agriculture, is shown to be highly efficient as an ionophore for Pb super(2+) and to be highly selective for Pb super(2+) compared with other divalent cations. Monensin transports Pb super(2+) by an electroneutral mechanism in which the complex PbMonOH is the transporting species. Electrogenic transport via the species PbMon super(+) may also be possible. Monensin catalyzed Pb super(2+) transport is little affected by Ca super(2+), Mg super(2+), or K super(+) concentrations that are encountered in living systems. Na super(+) 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 Pb super(2+) is consistent with the pattern of complex formation constants observed in the mixed solvent 80% methanol/water. This pattern also explains why Ca super(2+), Mg super(2+), and K super(+) are ineffective as inhibitors of Pb super(2+) transport, but it does not fully explain the actions of Na super(+), where kinetic features of the transport mechanism may also be important. When given to rats at 100 ppm in feed together with Pb super(2+) 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.