Brain (Na+, K+)-ATPase and noradrenergic activity: effects of hyperinnervation and denervation on high-affinity...

To examine the role of nerve-specific (Na+, K+)-ATPase in chronic changes in noradrenergic activity, we examined the effects of noradrenergic denervation and hyperinnervation on p-nitrophenylphosphatase activity and on total and nerve-specific ouabain binding. High-affinity and erythrosin B-sensitive binding were compared as measurements of nerve-specific binding. Hyperinnervation and denervation was produced in cerebellum and cerebral cortex, respectively, by 6-hydroxydopamine lesions of the dorsal noradrenergic bundle. Hyperinnervation increased, and denervation decreased, enzyme activity, high-affinity ouabain inhibition, and erythrosin B-sensitive ouabain binding. As (Na+, K+)-ATPase has a major role in the regulation of neural excitability and energy metabolism, and the ouabain binding site has been shown to have endogenous ligands, these changes in (Na+, K+)-ATPase may be important in the long-term regulation of neuron function by norepinephrine.