The blockade of low affinity neurotensin (nts2) receptor impairs brain nitric oxide synthesis and mitochondrial function

ANALIA G. KARADAYIAN; GEORGINA RODRÍGUEZ DE LORES ARNAIZ; SILVIA LORES ARNAIZ; ALICIA ANGELA GUTNISKY

Buenos Aires

Congreso; 2nd FALAN Congress 2016; 2016

Federation of Latinamerican Neuroscience Societies

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. Mitochondrial respiratory complexes activities were also determined. 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 46 % and 74% 30 min and 18 h after levocabastine administration. NOS expression decreased by 9% and 52% in synaptosomal mem¬branes 30 min and 18 hs after levocabastine treatment. NOS activity in mitochondria remained unaltered at 30 min but was 42% lower after 18 h of levocabastine administration. Mitochondrial complexes I-IV activities were severily decreased by levocabastine. NOS and mitochondrial complexes activities were also decreased after in vitro incubation of both fractions with 10-5M levocabastine. Results suggest that the activity of NTS2 receptor modulates synaptic NO synthesis and mitochondrial function at central nervous system.