Changes in Na+, K+-ATPase Activity and Alpha 3 Subunit Expression in CNS After Administration of Na+, K+-ATPase Inhibitors

The expression of Na+, K+-ATPase alpha 3 subunit and synaptosomal membrane Na+, K+-ATPase activity were analyzed after administration of ouabain and endobain E, respectively commercial and endogenous Na+, K+-ATPase inhibitors. Wistar rats received intracerebroventricularly ouabain or endobain E dissolved in saline solution or Tris-HCl, respectively or the vehicles (controls). Two days later, animals were decapitated, cerebral cortex and hippocampus removed and crude and synaptosomal membrane fractions were isolated. Western blot analysis showed that Na+, K+-ATPase alpha 3 subunit expression increased roughly 40% after administration of 10 or 100 nmoles ouabain in cerebral cortex but remained unaltered in hippocampus. After administration of 10 mu l endobain E (1 mu l = 28 mg tissue) Na+, K+-ATPase alpha 3 subunit enhanced 130% in cerebral cortex and 103% in hippocampus. The activity of Na+, K+-ATPase in cortical synaptosomal membranes diminished or increased after administration of ouabain or endobain E, respectively. It is concluded that Na+, K+-ATPase inhibitors modify differentially the expression of Na+, K+-ATPase alpha 3 subunit and enzyme activity, most likely involving compensatory mechanisms.