Norepinephrine and (Na+, K+)-ATPase: evidence for stabilization by lithium or imipramine

These experiments examined the effects of lithium and imipramine on the regulation by norepinephrine in vivo of (Na+, K+)-ATPase in brain and heart. The binding of ouabain and the activity of K+-phosphatase were used as indices of (Na+, K+)-ATPase. In the cerebral cortex, imipramine prevented, and lithium reduced, the increase in (Na+, K+)-ATPase associated with repeated injections of yohimbine. Imipramine and yohimbine had synergistic effects on the increased release of norepinephrine and on decreased binding to beta-receptors. Effects on the binding of beta-noradrenergic receptors suggested that imipramine partially reduced stimulation of ATPase by reducing the maximum effect of beta-receptors, while the effect of lithium may have involved a reduction in the exposure of receptors to norepinephrine. Imipramine also increased (Na+, K+)-ATPase in the cerebral cortex of reserpine-treated rats. These results suggest that lithium and imipramine, by different mechanisms, can stabilize fluctuations in the physiological consequences of binding to noradrenergic receptors.