THE ACTIVITY AND ALPHA 3 SUBUNIT EXPRESSION OF Na+, K+-ATPase IN CNS ARE MODIFIED BY ADMINISTRATION OF Na/K-ATPase INHIBITORS.

G. RODRÍGUEZ DE LORES ARNAIZ; C. PEÑA ; M. G. BERSIER.

Santa Fe, Nueva Méjico

Congreso; XXXXI Congreso de la Sociedad Americana de Neuroquímica (ASN); 2010

Sociedad Americana de Neuroquímica (ASN)

Ouabain and endobain E, respectively commercial and endogenous Na/K-ATPase inhibitors, modify ligand dizocilpine binding and subunit expression of NMDA receptor at CNS level. Synaptosomal membrane ATPase activity and the expression of Na/K-ATPase alpha 3 subunit were analyzed after intracerebroventricular administration of ouabain and endobain E. Wistar rats were injected stereotaxically with ouabain or endobain E dissolved in saline solution or Tris-HCl, respectively. Rats injected with the corresponding vehicles were processed to serve as controls. Two days later, animals were decapitated, cerebral cortex and hippocampus removed and tissues subjected to differential centrifugation to isolate crude and synaptosomal membrane fractions. The activity of Na/K-ATPase in synaptosomal membranes isolated from cerebral cortex diminished after administration of ouabain but increased after administration of endobain E. Western blot assays indicated 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 microl endobain E (1 microl = 28 mg tissue) Na/K-ATPase alpha 3 subunit enhanced 130% in cerebral cortex and 103% in hippocampus. It is concluded that the administration of Na/K-ATPase inhibitors modify differentially Na/K-ATPase activity and the expression of Na/K-ATPase alpha 3 subunit, most likely involving compensatory mechanisms.