Perturbation of alpha-aminoisobutyric acid transport in human placental membranes: direct effects by HgCl2, CH3HgCl, and CdCl2.
Mercuric chloride, methylmercuric chloride, and cadmium chloride directly affect the human placental syncytiotrophoblast microvillous membrane. These heavy metals alter the facilitated diffusion of alpha-aminoisobutyric acid (AIB) into vesicles of this membrane in microM concentrations. Mercuric chloride abolishes temporal kinetics of AIB transport, inducing an initial increase in AIB transport (27% at 100 microM) but subsequently lowering equilibrium values when compared to equilibrium time points in control. Methylmercuric chloride and cadmium chloride inhibited the initial rate of AIB transport (40% and 21%, respectively, at 200 microM), but did not affect the equilibrium value of AIB transported when compared to equilibrium levels in control. These effects were concentration dependent. Methylmercuric chloride was more potent in inhibiting AIB transport than cadmium chloride. Methylmercuric chloride and cadmium chloride effects on AIB transport were observed with minimal preincubation with placental vesicles. However, preincubation was necessary for mercuric chloride-induced perturbation of AIB transport. Cysteine protects against mercuric chloride- and methylmercuric chloride-induced effects on AIB transport but did not reverse these perturbations. Mercury- and cadmium-induced placental membrane toxicity result from interactions of these heavy metals with the placental plasma membranes.
D000621:Aminoisobutyric Acids / Q000378:metabolism*; D001692:Biological Transport / Q000187:drug effects; D002104:Cadmium / Q000494:pharmacology*; D019256:Cadmium Chloride; D002462:Cell Membrane / Q000378:metabolism*; D005260:Female; D006801:Humans; D007700:Kinetics; D008627:Mercuric Chloride; D008628:Mercury / Q000494:pharmacology*; D008767:Methylmercury Compounds / Q000494:pharmacology*; D008871:Microvilli / Q000187:drug effects / Q000378:metabolism*; D010920:Placenta / Q000187:drug effects / Q000378:metabolism*; D011247:Pregnancy
D000621:Aminoisobutyric Acids; D008767:Methylmercury Compounds; D002104:Cadmium; C100049:2-aminoisobutyric acid; D008627:Mercuric Chloride; D008628:Mercury; D019256:Cadmium Chloride; C004925:methylmercuric chloride