THE BLOCKADE OF LOW AFFINITY NEUROTENSIN (NTS2) RECEPTOR IMPAIRS BRAIN NITRIC OXIDE PRODUCTION AND MITOCHONDRIAL BIOENERGETICS.

A.G. KARADAYIAN; A. GUTNISKY; S. LORES ARNAIZ; G. RODRÍGUEZ DE LORES ARNAIZ.

Buenos Aires

Congreso; Segundo Congreso de la Federación de Sociedades Latinoamericanas de Neurociencias (FALAN); 2016

THE BLOCKADE OF LOW AFFINITY NEUROTENSIN (NTS2) RECEPTOR IMPAIRS BRAIN NITRIC OXIDE PRODUCTION AND MITOCHONDRIAL BIOENERGETICS.A.G. Karadayian, A. Gutnisky, S. Lores Arnaiz y G. Rodríguez de Lores Arnaiz.Segundo Congreso de la Federación de Sociedades Latinoamericanas de Neurociencias (FALAN), Buenos Aires, 17 al 20 de noviembre de 2016.Neurotensin is able to modulate ionic gradient equilibria through neuronal membranes because it inhibits the activity of the sodium pump. Some properties of Na+, K+-ATPase are modified by administration of NOS inhibitor L-NAME, and by levocabastine, an antagonist for neurotensinergic NTS2 receptor. In the search of a relationship between the activity of neurotensin NTS2 receptor and NO synthesis, levocabastine was administered to rats and the activity and expression of nitric oxide synthase (NOS) were evaluated. Wistar rats injected (i.p.) with levocabastine (50 μg/kg) or vehicle (controls) were decapitated 30 min or 18 hs later. Cerebral cortices were processed to obtain synaptosomal membrane and mitochondrial fractions by differential and gradient centrifugation. Synaptosomal NOS activity decreased respectively by 46 % and 74% 30 min and 18 h after levocabastine administration. nNOS expression decreased by 18% and 56% in synaptosomal membranes 30 min and 18 hs after levocabastine treatment. NOS activity in mitochondria remained unaltered at 30 min but was 42% lower at 18 hs after the treatment. Mitochondrial complexes I-IV activities were severely decreased by levocabastine. Significant decreases in NOS and in mitochondrial complexes activities were also observed after in vitro incubation of both fractions with 10-5M levocabastine. Results suggest that the activity of NTS2 receptor modulates NO function at central nervous system.