Interaction between metals and chelating agents affects glutamate binding on brain synaptic membranes

The present study investigates the possible effects of Hg2+, Pb2+, and Cd2+ on [H-3]-glutamate binding. To better understand the role of the thiol-disulfide status on the toxicity of such metals toward glutamatergic neurotransmission, we used three thiol chelating agents, 2,3-dimercapto-propanol (BAL), 2,3-dimercaptopropane 1-sulfonate (DMPS), and meso-2,3-dimercaptosuccinic acid (DMSA). Dithiotreitol (DTT) was tested for its ability to prevent metals-induced inhibition on [H-3]-glutamate binding. Hg2+, Pb2+, and Cd2+ showed a concentration-dependent inhibition on [H-3]-glutamate binding, and mercury was the most effective inhibitor. BAL did not prevent [H-3]-glutamate binding inhibition by Hg2+, Cd2+, and Pb2+. However, DMPS and DMSA prevented the inhibition caused by Cd2+ and Pb2+, but not by Hg2+. DTT did not prevent the inhibition on [H-3]-glutamate binding caused by 10 muM Hg2+. In contrast, it was able to partially prevent [H-3]-glutamate binding inhibition caused by 40 muM Pb2+ and Cd2+. These results demonstrated that the heavy metals present an inhibitory effect on [H-3]-glutamate binding. In addition, BAL was less effective to protect [H-3]-glutamate binding inhibition caused by these metals than other chelating agents studied.