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© 1981 Oxford University Press

research-article

The Effects of Select Neurotoxic Chemicals on Synaptosomal Monoamine Uptake and K+-Dependent Phosphatase

WILLIAM M. BRACKEN, RAGHUBIR P. SHARMA and STEPHEN J. KLEINSCHUSTER

Toxicology Program and Department of Animal, Dairy & Veterinary Sciences, Utah State University Logan, Utah 84322

The Effects of Select Neurotoxic Chemicals on Synaptosomal Monoamine Uptake and K+-Dependent Phosphatase. Bracken, William M., Sharma, Raghubir P. and Kleinschuster, Stephen J. (1981). Fundam. Appl. Toxicol. 1:432–436. The in vitro inhibition of norepinephrine (NE) and serotonin (5-HT) uptake into rat brain synaptosomes by a diverse group of neurotoxic chemicals was studied. The test chemicals included CH3HgCl, Hg(NO3)2, CdCl2, diisopropylfluorophosphate (DFP), paraoxon, acrylamide and Kepone while chlorpromazine and ouabain were used as reference chemicals. Methylmercuric chloride, Hg(NO3)2 and Kepone inhibited the NE and 5-HT uptake with IC50's (concentration of chemical inhibiting 50% of uptake) between 10–4 to 10–3 M for both amines. Maximal inhibition was 60–100% at 10 3 M. Cadmium chloride, paraoxon, DFP and acrylamide were not inhibitory. The influence of the test chemicals on synaptosomal K+-dependent phosphatase was studied. Methylmercuric chloride, Hg(NO3)2, CdCl2 and Kepone were inhibitors of the phosphatase with 50% inhibition (I50) at micromolar concentrations. The phosphatase was most sensitive to Hg(NO3)2 inhibition with an I50 of 0.03 /M. The inhibitory concentrations for these chemicals ranged from 10–7 to 10–3 M. A correlation of the phosphatase and monoamine uptake inhibitions was not suggested from the data. The low affinity inhibition (IC50 greater than 10(–5 M) of the NE and 5-HT uptake by CH3HgCl, Hg(NO3)2 and Kepone suggested that this is not a biologically important phenomena. The apparent high affinity inhibition (I50 less than 10–5 M) of the phosphatase demonstrated the specific influences the test compounds can have on enzymatic processes. Such enzymatic inhibition would be of critical importance if these neurotoxicants were able to penetrate the synaptic or neuronal membrane.


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