Impairment of nitric oxide metabolism at central synapses by levocabastine, an antagonist for neurotensinergic NTS2 receptor

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

Buenos Aires

Congreso; Reunión Conjunta de Sociedades de Biociencias; 2017

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 the administration of L-NAME (Nω-nitro-L-arginine methyl ester), an inhibitor of nitric oxide synthase (NOS), 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 nitric oxide (NO) synthesis, levocabastine was administered to rats and the activity and expression of NOS were evaluated. Wistar rats injected (i.p.) with levocabastine (50 μg/kg) or saline solution (controls) were decapitated 30 min, 18 or 36 hours later. Cerebral cortices were processed by differential and sucrose gradient centrifugation to obtain synaptosomal mem¬brane fractions. Nitric oxide production by NOS was measured following the oxidation of oxyhemoglobin to methemoglobin at 577-591 nm in a double-beam dual-wavelength spectrophotometer. Neuronal and inducible NOS expression were evaluated by Western blot assays. In synaptosomal mem¬brane fractions NOS activity decreased 46% and 74% at 30 min and 18 hours after levocabastine administration (p