(Na+,K+)-ATPase and noradrenergic regulation: effects of cardiac glycoside treatment and noradrenergic manipulations.

We examined effects of treatment with cardiac glycosides, in combination with noradrenergic stimulation or depletion, on (Na+,K+)-ATPase activity in rat cerebral cortex, heart, and kidney. Treatment with digitoxin increased the apparent number of (Na+,K+)-ATPase sites in heart, cerebral cortex, and kidney. Ouabain, which crosses the blood-brain barrier poorly, did not affect enzyme in brain but was otherwise similar. Norepinephrine depletion prevented the increase in heart but not in cerebral cortex. Noradrenergic stimulation increased the number of sites in cerebral cortex and in heart. In rats treated with digitoxin, noradrenergic stimulation increased enzyme activity further in heart but not in cerebral cortex. Examination of effects on noradrenergic receptor binding and on norepinephrine metabolite concentrations suggested that, while in heart cardiac glycosides appeared to increase norepinephrine release, in brain there was no effect on release but there may have been appreciable inhibition of norepinephrine reuptake under stimulated conditions.