The effect ofin vitro andin vivo ethylenbis dithiocarbamate fungicides on NMDA receptors in rat brain membranes

Abstract

To determine whether the ethlenbisdithiocarbamate fungicides, zineb, manzeb and maneb affect the N-methyl-D-aspartate (NMDA) receptor in rat brain membranes, we performed a binding assay using [(3)H]MK-801, a noncompetitive NMDA receptor antagonist. Displacement studies were conducted using well washed membranes to exclude the effect of endogenous acidic amino acids on the binding of [(3)H]MK-801. In both the presence or absence of added glutamate and glycine in the assay buffer, the dose-response curve indicated that zineb enhanced the binding in a concentration range of 100-500 μM. However, the displacement curves indicated that manzeb and maneb inhibited the binding in a concentration range of 10-500 μM. The addition of 50 μM glutamate and glycine to the assay medium increased binding by 5-20% above the control in a concentration range of 0.1-100 μM.No rats injected with zineb, manzeb, maneb (100 mg/kg, ip) showed any characteristic toxic signs or any significant weight changes within 24 hrs. Estimation of [(3)H]MK-801 binding to unwashed membranes from intoxicated rat brains revealed no marked change in Bmax or Kd values for 24 hrs following fungicide administration.