Monensin mediates a rapid and selective transport of Pb(2+). Possible application of monensin for the treatment of Pb(2+) intoxication.
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 approximately 50%. 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.
Hamidinia
Shawn A
SA
Department of Molecular and Cellular Biochemistry, Ohio State University, Columbus, Ohio 43210, USA.
Shimelis
Olga I
OI
Tan
Bo
B
Erdahl
Warren L
WL
Chapman
Clifford J
CJ
Renkes
Gordon D
GD
Taylor
Richard W
RW
Pfeiffer
Douglas R
DR
D000818:Animals; D001692:Biological Transport / Q000502:physiology*; D002264:Carboxylic Acids / Q000378:metabolism; D002413:Cations, Divalent / Q000378:metabolism; D006863:Hydrogen-Ion Concentration; D007476:Ionophores / Q000494:pharmacology*; D007854:Lead / Q000008:administration & dosage / Q000378:metabolism*; D008297:Male; D015394:Molecular Structure; D008985:Monensin / Q000008:administration & dosage / Q000494:pharmacology*; D011897:Random Allocation; D051381:Rats; D022161:Transport Vesicles / Q000737:chemistry / Q000378:metabolism
D002264:Carboxylic Acids; D002413:Cations, Divalent; D007476:Ionophores; D007854:Lead; D008985:Monensin