IMPAIRMENT OF NITRIC OXIDE METABOLISM AT CENTRAL SYNAPSES BY LEVOCABASTINE, AN ANTAGONIST FOR NEUROTENSINERGIC NTS2 RECEPTOR

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

Buenos Aires

Congreso; Primer Congreso de Ciencias Biomédicas; 2017

SAIC-SAFE-SAFIS-SAB

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 between 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 membrane 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