The inhibition of cerebral high affinity receptor sites by lead and mercury compounds

Abstract

Abstract. 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.

Effects of triethyl lead on various cholinergic parameters in the rat brain in vitro.

“…The inhibition by triethyl Pb in the present experiments, in the presence of 0.3 to 1.0 nM [3H]QNB, was similar to that by tri-n-butyl lead reported by Bondy and Agrawal (13). The mechanisms of the inhibition by organolead are generally accepted to involve interactions with amino acid residues or SH gourp(s) within the allosteric binding sites of the receptor molecule (13).…”

“…Bondy and Agrawal (13) reported that tri-nbutyl lead acetate inhibited the binding of [3H]QNB to membranes from rat brain in the presence of 1 nM QNB. The inhibition by triethyl Pb in the present experiments, in the presence of 0.3 to 1.0 nM [3H]QNB, was similar to that by tri-n-butyl lead reported by Bondy and Agrawal (13).…”

“…Bondy and his colleagues (11)(12)(13) reported that tri-n-butyl lead inhibited the high-affinity uptake of choline (HACU) and the binding of…”

Animal Biomarkers as Pollution Indicators

“…A list of the possible plasma receptors is given in Table 9.3. The affinity of the dopamine receptor for dopamine has been shown to be decreased by lead and mercury (Bondy and Agrawal, 1980). The muscarinic cholinergic receptor that binds acetylcholine is easily separated and has been well characterized.…”

Evaluation of the Effects of Chronic Intoxication with Inorganic Mercury on Memory and Motor Control in Rats

“…, thiol groups of proteins, peptides and amino acids), interactions of mercury compounds with proteins in the CNS may explain some of their effects on neurotransmission. Mercury micromolar concentrations inhibited cholinergic, glutamatergic, GABAergic and dopaminergic systems [ 47 , 48 , 49 , 50 , 51 ], affecting both behavior and cognition. It is well established that cognitive and motivational processes depend on the connections between PFC and limbic structures, which are dependent on the neurotransmitters cited above, and the hippocampus plays a key role in the functioning of these pathways [ 43 ].…”