Brain (Na+,K+)-ATPase and noradrenergic function: recovery of enzyme activity after norepinephrine depletion

We examined the time course of K+-p-nitrophenylphosphatase and ouabain binding associated with cerebral cortex (Na+,K+)-AT-Pase after depletion of norepinephrine. Norepinephrine depletion by the norepinephrine-selective neurotoxin DSP4 initially reduced the indices of (Na+,K+)-ATPase, with a significant correlation between ouabain binding and tissue norepinephrine levels 16 h after DSP4. Tissue norepinephrine content and DMI binding rapidly declined after DSP4 and remained essentially unchanged for at least 8 weeks. By contrast, the indices of (Na+,K+)-ATPase remained low for about two weeks but then gradually increased, returning to baseline levels by 8 weeks after DSP4. These data indicate that, while usually regulated in part by exposure to norepinephrine, brain (Na+,K+)-ATPase undergoes adaptation to prolonged noradrenergic depletion.