Norepinephrine-stimulated increase in Na+, K+-ATPase activity in the rat brain is mediated through alpha1A-adrenoceptor possibly by dephosphorylation of the enzyme.

Rapid eye movement sleep deprivation is reported to increase Na+,K+-ATPase activity. This increase was shown earlier to be stimulated by norepinephrine acting on alpha1-adrenoceptor. The involvement of a subtype of alpha1-adrenoceptor and the possible molecular mechanism of action of norepinephrine in increasing the enzyme activity were investigated using receptor agonists and antagonists, as well as stimulants and blockers of signal transduction pathway. It was observed that incubation of the homogenate with cyclic AMP, forskolin, A23187 (a calcium ionophore), or calmodulin alone did not stimulate the Na+,K+-ATPase activity. However, although the spontaneous activity of the Na+,K+-ATPase was not affected by prazosin, WB4101, heparin, W13, or cyclosporin A alone, each of them could prevent the norepinephrine-stimulated increase in the enzyme activity. Based on these results and our previous findings, it is proposed that norepinephrine acted on alpha1A-adrenoceptor and increased intracellular calcium, which in the presence of calmodulin activated a calmodulin-dependent phosphatase, calcineurin. This calcineurin possibly dephosphorylated Na+,K+-ATPase and increased its activity. The physiological significance especially in relation to rapid eye movement sleep deprivation is discussed.