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Neurotensin inhibits Na+, K+-ATPase activity present in synaptosomal membranes isolated from rat cerebral cortex. This effect occurs through high affinity neurotensin receptor (NTS1). The presence of neurotensin (agonist) or SR 48692 (Sanofi-Aventis, U.S., Inc.), a non-peptidic antagonist for high affinity neurotensin receptor (NTS1) in the incubation medium decrease high affinity [3H]-ouabain binding to CNS membranes (SAFE, 2008). In order to explore potential participation of NTS1 receptor activation on such effect, assays were carried out in vitro and after administration of the antagonist. Rat cerebral cortex membranes were incubated with [3H]-ouabain in the presence of neurotensin and / or SR 48692 solutions, to obtain additive or synergic effects, according to the concentration employed. Lots of rats were administered i.p. with SR 48692 (dissolved in saline solution with 0.01% Tween 80) and were decapitated 30 min later. Rats injected with vehicle were processed in parallel to serve as controls. [3H]-ouabain binding was statistically significantly decreased after administration of 250 ìg / kg SR 48692. In cortical membranes isolated from rats previously injected with SR 48692, neurotensin added during [3H]-ouabain binding assay decreased binding in a way similar to that recorded in the vehicle injected controls. Saturation assays followed by Scatchard analyses showed increase in Kd value but no change in Bmax value. Results suggested that neurotensin acts as a competitive inhibitor of high affinity [3H]-ouabain binding. The antagonist for NTS1 receptor not only failed to block neurotensin effect but also produced an inhibitory effect itself on [3H]-ouabain binding to CNS membranes.