The inhibition of cerebral high affinity receptor sites by lead and mercury compounds.
The effect of various concentrations of several lead and mercury compounds upon various high affinity receptor sites within discrete brain regions has been measured. The specific binding of radioactive spiroperidol and quinuclidinyl benzilate to striatal and cortical membranes respectively, was much more severely inhibited in the presence of tri-n-butyl lead acetate than by lead acetate. This suggested that the hydrophobic organic lead derivative was able to interfere with receptor structure more readily than the lead acetate. On the other hand mercuric chloride was more effective in blocking these two neurotransmitter receptor sites than was the organic methylmercuric chloride. This implied that sulfhydryl groups may be within, or proximal to the allosteric binding site. The relative ineffectiveness of all heavy metal compounds studied in blocking the glycine. GABA or the diazepam receptors indicated that the mechanism of binding may not be similar with different receptor proteins. Since micromolar concentrations of some lead and mercury compounds suffice to severely inhibit neurotransmitter binding sites, such a direct interference with postsynaptic events may in part account for the neurological consequences of heavy metal poisoning.
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D007854:Lead / Q000633:toxicity*; D008297:Male; D008628:Mercury / Q000633:toxicity*; D018377:Neurotransmitter Agents / Q000378:metabolism; D051381:Rats; D017981:Receptors, Neurotransmitter / Q000187:drug effects*
D018377:Neurotransmitter Agents; D017981:Receptors, Neurotransmitter; D007854:Lead; D008628:Mercury