Effect of tributyltin on the N-methyl-D-aspartate (NMDA) receptors in the mouse brain

The purpose of this study was to determine the effect of tributyltin chlori de (TBTCl) on the NMDA receptor by in vitro and in vivo experiments. In the first in vitro experiment, the binding of [H-3]MK-801 and of [H-3]-CGP3965 3 were studied in membrane preparations from the cerebral cortex of intact mice to obtain control values. Saturation experiments for [H-3]MK-801 and [ H-3]CGP39653 revealed single binding sites with K-d values of 10.27 and 37. 8 nM, and receptor densities of 1.75 and 2.20 pmol/mg of protein, respectiv ely. In the second in vitro experiment, displacement studies were carried o ut with TBTCl over a concentration range of 0.1 muM to 2 mM. TBTCl inhibite d [H-3]MK-801 binding but did not affect [H-3]CGP39653 binding. In the in v ivo experiments, the mice received 1-125 ppm TBTCl in the diet ad libitum f or 30 days. Ligand binding to cortical membrane preparations from each mous e was measured by a one-concentration point (2 nM) binding assay. [H-3]MK-8 01 binding was significantly lowered (P < 0.05) in the 5 and 125 ppm TBTCl- exposed animals compared with the controls. [H-3]CGP39653 binding was also significantly lowered (P < 0.05) in the 1 and 125 ppm TBTCl-exposed animals compared with the controls. These results suggest that the NMDA receptors in the mouse brain are sensitive to relatively low level exposure to TBTCl.