The blockade of low affinity neurotensin (NTS2) receptor impairs brain nitric oxide production and mitochondrial bioenergetics.

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

Buenos Aires

Congreso; 2nd Federation of Latinamerican Neuroscience Societies (FALAN) Congress 2016; 2016

Sociedad Argentina de Investigación en Neurociencias - Federation of Latin American and Caribbean 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. NOS activity decreased by 46% and 74% in synaptosomal membranes after 30 min and 18 h levocabastine administration respectively. NOS expression decreased by 18% and 56% 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 respiratory capacity and complexes I-IV activities were strongly decreased by levocabastine. Results suggest that the activity of NTS2 receptor modulates synaptic NO production and mitochondrial function at central nervous system.