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 ³H]-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-dimercaptopropanol (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 ³H]-glutamate binding. Hg²⁺, Pb²⁺, and Cd²⁺ showed a concentration-dependent inhibition on ³H]-glutamate binding, and mercury was the most effective inhibitor. BAL did not prevent ³H]-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 ³H]-glutamate binding caused by 10 M Hg²⁺. In contrast, it was able to partially prevent ³H]-glutamate binding inhibition caused by 40 M Pb²⁺ and Cd²⁺. These results demonstrated that the heavy metals present an inhibitory effect on ³H]-glutamate binding. In addition, BAL was less effective to protect ³H]-glutamate binding inhibition caused by these metals than other chelating agents studied.