Monensin Mediates a Rapid and Selective Transport of Pb2+

Abstract

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 Pb 2؉ and to be highly selective for Pb 2؉ compared with other divalent cations. Monensin transports Pb 2؉ 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 Pb 2؉ transport is little affected by Ca 2؉ , Mg 2؉ , or K ؉ concentrations that are encountered in living systems. Na ؉ is inhibitory, but its effectiveness at 100 mM does not exceed ϳ50%. The poor activity of monensin as an ionophore for divalent cations other than Pb 2؉ is consistent with the pattern of complex formation constants observed in the mixed solvent 80% methanol/water. This pattern also explains why Ca 2؉ , Mg 2؉ , and K ؉ are ineffective as inhibitors of Pb 2؉ 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 Pb 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.

Synthesis, structure and antimicrobial activity of manganese(II) and cobalt(II) complexes of the polyether ionophore antibiotic Sodium Monensin A

“…Consistent with its mode of action, the effectiveness of Monensin appears to be sensitive to the local cation environment [22][23][24][25][26]. Very recently it was shown that polyether antibiotics are highly effective as ionophores for Pb 2+ and could react with a broad range of cations not just monovalent ones as often assumed [27][28][29][30].…”

Crystal structure and properties of the copper(II) complex of sodium monensin A

“…Although there is some evidence that monensin reacts with divalent metal ions, only a limited number of research teams are studying the antibiotic reactions with metal ions other than monovalent representatives [33][34][35][36][37][38][39].…”

Selective transport of Pb2+ and Cd2+ across a phospholipid bilayer by a cyclohexanemonocarboxylic acid-capped 15-crown-5 ether

“…2 compares the transport activity of P3CA-15C5 to that of monensin [13] and ionomycin [12]. The concentrations of the ionophores were chosen to ensure that the rates of cation transport occurred on a reasonable time scale (e.g., 5-15 min.).…”

“…1), transport Pb 2+ across biological membranes with high selectivity over other divalent cations [12][13][14], and that they can enhance the elimination of Pb 2+ from cultured cells [12] and rats [13]. Although these naturally occurring compounds have favorable transport properties, their structures are difficult to modify in a systematic fashion.…”

“…Based on their results, we selected P3CA-15C5 for more detailed studies using a well-defined phospholipid vesicle system that provides a more realistic model of biological membranes [21,22]. Our group and others have used this type of system to study the selectivity and mechanisms of cation transport mediated by other ionophores [12][13][14][21][22][23][24][25][26][27]. In this paper, we report the results of transport studies which show that P3CA-15C5 is an effective and selective ionophore for Cd 2+ and Pb 2+ , and that the predominant transport mechanisms in phospholipid bilayer membranes are electrogenic.…”