The effects of DDT, DDOH-palmitic acid, and a chlorinated paraffin on muscarinic receptors and the sodium-dependent choline uptake in the central nervous system of immature mice.
Ten-day-old NMRI mice were given a single peroral dose of 1.4 mumol/kg body wt of either of the substances of DDT (0.5 mg), DDOH-PA (a DDT metabolite conjugated to palmitic acid; 0.7 mg), or polychlorohexadecane (PCHD, a synthesized chlorinated paraffin; 1.0 mg). The mice were killed either 24 hr or 7 days after treatment, and crude synaptosomal fractions (P2) were prepared from the cerebral cortex and hippocampus. The density of the muscarinic receptors was assayed by measuring quinuclidinyl benzilate ([3H]QNB) specifically bound in the P2 fraction. A significant increase in the specific [3H]QNB binding was observed in the cerebral cortex in DDT- and DDOH-PA-treated mice 7 days after treatment, compared to control. These results were further explored by determining the ratio of high- and low-affinity binding sites by using an agonist (carbachol)-antagonist ([3H]QNB) competition assay. A significant decrease in the percentage of high-affinity binding sites and a corresponding increase in the percentage of low-affinity binding sites, compared to control, were observed after DDT and DDOH-PA treatment. The presynaptically sodium-dependent choline uptake system also was studied. In mice receiving PCHD there was a significant decrease (65%) in the Vmax value 7 days after treatment, but no change was observed in mice receiving DDT or DDOH-PA. This study shows that the sensitivity of the cholinergic system to persistent xenobiotics acting over a long period of time may be higher in the immature mouse.
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002794:Choline / Q000378:metabolism*; D003634:DDT / Q000031:analogs & derivatives* / Q000633:toxicity*; D005260:Female; D008297:Male; D051379:Mice; D010169:Palmitic Acids / Q000633:toxicity*; D010232:Paraffin / Q000633:toxicity*; D011976:Receptors, Muscarinic / Q000032:analysis / Q000187:drug effects*; D012964:Sodium / Q000494:pharmacology*
D010169:Palmitic Acids; D011976:Receptors, Muscarinic; C050076:2,2-bis(4-chlorophenyl)ethanol-palmitic acid; D010232:Paraffin; D012964:Sodium; D003634:DDT; D002794:Choline