PT  - JOURNAL ARTICLE
AU  - Takahiro Yanagiya
AU  - Nobumasa Imura
AU  - Shuichi Enomoto
AU  - Yukihiro Kondo
AU  - Seiichiro Himeno
TI  - Suppression of a High-Affinity Transport System for Manganese in Cadmium-Resistant Metallothionein-Null Cells
DP  - 2000 Mar 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 1080--1086
VI  - 292
IP  - 3
4099  - http://jpet.aspetjournals.org/content/292/3/1080.short
4100  - http://jpet.aspetjournals.org/content/292/3/1080.full
SO  - J Pharmacol Exp Ther2000 Mar 01; 292
AB  - Cadmium is a hazardous heavy metal existing ubiquitously in the environment, but the mechanism of cadmium transport into mammalian cells has been poorly understood. Recently, we have established a cadmium-resistant cell line (Cd-rB5) from immortalized metallothionein-null mouse cells, and found that Cd-rB5 cells exhibited a marked decrease in cadmium uptake. To investigate the mechanism of altered uptake of cadmium in Cd-rB5 cells, incorporation of various metals was determined simultaneously using a multitracer technique. Cd-rB5 cells exhibited a marked decrease in manganese incorporation as well as that of cadmium. However, the reduced uptake of manganese was observed only at low concentrations, suggesting that a high-affinity component of the Mn2+ transport system was suppressed in Cd-rB5 cells. Competition experiments and kinetic analyses revealed that low concentrations of Cd2+ and Mn2+ share the same high-affinity pathway for their entry into cells. The mutual competition of Cd2+ and Mn2+ uptake was also observed in HeLa, PC12, and Caco-2 cells. The highest uptake of Cd2+ and Mn2+ by parental cells occurred at neutral pH, suggesting that this pathway is different from a divalent metal transporter 1 that can transport various divalent metals including Cd2+ and Mn2+ under acidic conditions. These results suggest that a high-affinity Mn2+transport system is used for mammalian cellular cadmium uptake, and that the suppression of this pathway caused a marked decrease in cadmium accumulation in cadmium-resistant metallothionein-null cells. The American Society for Pharmacology and Experimental Therapeutics