Brain Na,K-ATPase: Regulation by Norepinephrine and an Endogenous Inhibitor

Publisher Summary This chapter discusses the regulation of brain Na, K-ATPase by Norepinephrine and an endogenous inhibitor. One important question about Na, K-ATPase is whether there are specific mechanisms whereby populations of enzyme molecules having specialized physiologic functions are regulated. The possible presence of two enzyme forms raises the question of whether they are differentially regulated by physiologic enzyme effectors. A compound in brain extracts and plasma that reduces cardiac glycoside binding, cation transport, and enzyme activity is one candidate for such an effector, especially because the endogenous inhibitor appears to interact with the cardiac glycoside binding site and affinity for cardiac glycosides may distinguish the two enzyme forms. The experiments reported in the chapter examine: (1) the interactions of endogenous inhibitor and norepinephrine with high-affinity ouabain binding, (2) interactions between norepinephrine and endogenous inhibitor in vitro , and (3) the effects of persistent changes in exposure to norepinephrine in vivo on high-affinity ouabain binding. The material in brain extract reduced stimulation of enzyme activity by norepinephrine, decreasing maximal stimulation 3-fold and apparent affinity 10-fold.