High affinity receptors but not low affinity receptors for neurotensin are involved in neuronal Na/K-ATPase inhibition by the peptide

Abstract

Neurotensin acts as a neuromodulator or as a neurotransmitter that binds to a group of receptors. Two of the receptors, namely NTS1 and NTS2, bind to neurotensin with high affinity and low affinity, respectively. Neurotensin added in vitro inhibits synaptosomal membrane Na+ , K+ - ATPase activity. This effect seems to be mediated by NTS1 receptor because it is fully blocked by antagonist SR 48692. Herein neurotensin effect was assayed after administration of SR 48692 and levocabastine which are antagonists for NTS1 and NTS2 receptors, respectively. Male Wistar rats were administered by i.p. injection, with 150 µg/kg SR 48692 (Sanofi-Aventis U.S., Inc.) suspended in the vehicle (0.01% Tween 80 in saline solution), 50 μg/kg levocabastine (disolved in saline solution) and the corresponding vehicle solutions. Thirty minutes later, the animals were sacrificed, cerebral cortices removed, separately pooled, and processed to obtain synaptosomal membranes. In membrane samples, Na+ , K+ - and Mg2+-ATPase activities were determined in the absence and presence of 3.5 x 10-6 M neurotensin. Basal Na+ , K+ -ATPase activity in membranes isolated from control rats (vehicle injected) decreased roughly by 60% by the peptide. This effect was entirely prevented by the administration of NTS1 antagonist SR 48692. Administration of levocabastine, which enhanced basal Na+ , K+ - ATPase activity, failed to prevent neurotensin inhibitory effect on this enzyme activity. Mg2+- ATPase activity remained unaltered in all conditions tested. It is concluded that Na+ , K+ - ATPase inhibition by neurotensin seems mediated only by NTS1 receptor because the administration of NTS1 antagonist SR 48692, and not the NTS2 antagonist levocabastine prevented the effect of the peptide.Fil: Alvarez Juliá, Anabel. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia ; ArgentinaFil: Gutnisky, Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia ; ArgentinaFil: López Ordieres, María Graciela. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia ; Argentina. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; ArgentinaFil: Rodriguez, Georgina Emma. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia ; Argentin