Influence of pyridine and urea on the rat brain ATPase activity

The neurotoxicity of pyridine and urea was investigated in respect to their ability to alter the activity of synaptosomal membrane Na+/K(+)-ATPase and Mg(2+)-ATPase. In vitro treatment with pyridine and urea stimulated Na+/K(+)-ATPase activity in a dose-dependent manner up to 40% and 60%, respectively. Mg(2+)-ATPase activity increased up to 40% after pyridine treatment, while urea had no effect at all. The neuroactive potencies of pyridine and urea were evaluated by estimating parameters Km and delta Vmax for enzyme stimulation, as well as Hill coefficient to estimate the levels of cooperativity for pyridine and urea binding. The results suggest that pyridine stimulates both enzymes, probably by interacting with some neuronal membrane components, and altering the lipid micro-environment of the ATPases. In contrast, urea stimulates the Na+/K(+)-ATPase only, assumingly by acting on it directly or via some other regulatory mechanism. Stimulation of Na+/K(+)-ATPase and Mg(2+)-ATPase by the substances tested and subsequent alteration of neuronal cell functioning could contribute to the CNS dysfunction upon chronic exposure to pyridine and urea.