The Effect of \it{in Vitro} and \it{in Vivo} Ethylenbis Dithiocarbamate Fungicides on NMDA Receptors in Rat Brain Membranes
10.1265/ehpm.6.54
- Author:
Nobuhiro KONNO
;
Masashi TSUNODA
;
Kyoko NAKANO
- Publication Type:Journal Article
- Keywords:
zineb;
maneb;
manzeb;
NMDA receptor;
neurotoxicity
- MeSH:
binding;
Upper case emm;
Fungicide, NOS;
MK-801;
assay
- From:Environmental Health and Preventive Medicine
2001;6(1):54-59
- CountryJapan
- Language:Japanese
-
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 [3H]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 [3H]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 [3H]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.
