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

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

BUENOS AIRES

Congreso; SEGUNDO CONGRESO DE LA FEDERACIÓN DE SOCIEDADES DE NEUROCIENCIAS DE LATINOAMERICA Y EL CARIBE; 2016

Federación de Sociedades Latinoamericanas de Neurociencias (FALAN),

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 be¬tween the activity of neuro¬tensin 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 mem¬brane and mitochondrial fractions by differential and gradient centrifugation. Synaptosomal NOS activity decreased respectively by xx % and xx% 30 min and 18 h after levocabastine administration. nNOS expression decreased by xx% and xx% in synaptosomal mem¬branes 30 min and 18 hs after levocabastine treatment. NOS activity in mitochondria remained unaltered at 30 min but was xx% lower at 18 hs after the treatment. Mitochondrial complexes I-IV activities were severily 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.