ABSTRACT
The studies were performed to investigate the mechanism of phenamiphos affecting muscarinic acetylcholine receptor (M-AchR) of the brain synaptosome in rats. The results showed that phenamiphos inhibited the binding of 3H-quinuclidinyl benzilate (3H-QNB) to the brain synaptosome in rats, and this effect was dose and time-dependent. This suggests that phenamiphos might directly affect M-AchR. The KD and Bmax of phenamiphos to M-AchR were measured and found to be 1.3 x 10(-7) mol/L and 4.57 pmol/mg protein, respectively. It belongs to non-specific inhibition of phenamiphos on the binding of 3H-QNB to M-AchR. It was also found that phenamiphos decreased the level of protein sulfhydryl group in brain synaptosome membrane. Dithiothreitol (DTT) and the reduced glutathion (GSH) prevented the decrease of protein sulfhydryl group and the inhibition of phenamiphos on the binding of 3H-QNB to M-AchR. These showed that phenamiphos could affect the sulfhydryl group of M-AchR surface.
Subject(s)
Brain/metabolism , Insecticides/toxicity , Organophosphorus Compounds/toxicity , Receptors, Muscarinic/drug effects , Animals , Female , Male , Quinuclidinyl Benzilate/metabolism , Rats , Rats, Sprague-Dawley , Sulfhydryl Compounds/metabolism , Synaptosomes/metabolismABSTRACT
Effects of trifluoroacetic acid (TFA) on cell growth, DNA, glycoprotein, and dolichol-linked oligosaccharides synthesis and ribonucleotide triphosphate concentrations were examined in exponentially growing C6 murine glioma cells. One day of treatment with TFA caused a slight concentration-dependent enhancement of cell growth and [3H]thymidine incorporation. Exposure for 1 or 5 d to TFA (0.5-7.0 mM) elevated the [3H]leucine incorporation in a dose- and time-dependent manner. The results suggested that TFA stimulated cell growth and enhanced protein synthesis. TFA also affected [3H]mannose incorporation into glycoproteins and dolichol-linked oligosaccharides in a dose-dependent fashion. In addition, it was found that TFA accelerated lectin-induced cell agglutination. These data suggest that TFA, the principle halothane metabolite, alters plasmalemmal glycoprotein synthesis. These findings should form a basis for further understanding on the mechanism underlying halothane-associated neurotoxicity.
Subject(s)
Glioma/metabolism , Glycoproteins/biosynthesis , Oligosaccharides/biosynthesis , Trifluoroacetic Acid/pharmacology , Animals , Cell Division/drug effects , DNA, Neoplasm/drug effects , DNA, Neoplasm/metabolism , Glioma/pathology , Glycosylation/drug effects , Leucine/metabolism , Mannose/metabolism , Mice , Thymidine/metabolism , Tumor Cells, Cultured/drug effectsABSTRACT
Methyl-ISP, a newly developed organophosphorous insecticide, is used in China to treat and protect plants from pest infestation. Our studies demonstrated that methyl-ISP is metabolized rapidly in rat and mouse. Its toxicity was low, no obvious accumulative toxicity, chronic toxicity, teratogenicity, mutagenicity, reproductive toxicity or delayed neurotoxicity could be observed. It is therefore concluded that methyl-ISP is relatively safe to animals and human subjects. methyl-ISP is now employed to replace the other commonly used insecticide hexachlorobenzene (666) in agriculture. A preliminary study was performed to elucidate the mechanism of intoxication at subcellular levels.
