THE BLOCKADE OF NEUROTENSINERGIC NTS2 RECEPTOR INHIBITS NITRIC OXIDE PRODUCTION AND ENHANCES NORADRENALINE UPTAKE AT CNS

A. GUTNISKY; G. RODRÍGUEZ DE LORES ARNAIZ; A.G. KARADAYIAN; M. VATTA ; S. LORES ARNAIZ ; S. HOPE

Denver, Colorado

Congreso; 47th Annual Meeting of the American Society for Neurochemistry; 2016

American Society for Neurochemistry

THE BLOCKADE OF NEUROTENSINERGIC NTS2RECEPTOR INHIBITS NITRIC OXIDE PRODUCTION ANDENHANCES NORADRENALINE UPTAKE AT CNS Silvia Lores Arnaiz, Analía G. Karadayian, Alicia GutniskySandra Hope, Marcelo VattaGeorgina Rodríguez de Lores Arnaiz Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Instituto de Bioquímica y Medicina Molecular(IBIMOL, UBA-CONICET), Buenos Aires, Argentina Universidad de Buenos Aires, Facultad de Medicina, Instituto deBiología Celular y Neurociencias Prof. E. De Robertis (IBCN,UBA-CONICET), Buenos Aires, Argentina Universidad de Buenos Aires, Facultad de Farmacia y Bioquímica, Cátedra de Fisiología, IQUIMEFA (UBA-CONICET),Buenos Aires, ArgentinaNeurotensin behaves as a neuromodulator or as a neurotransmitterinteracting with NTS1 and NTS2 receptors, which bind the peptidewith high and low affinity, respectively. Neurotensin modulates Na/K-ATPase activity, an essential enzyme for the maintenance of ionicgradients. Na/K-ATPase properties can be modified by the administrationof L-NAME, an inhibitor of nitric oxide (NO) synthesis andby levocabastine, an antagonist for NTS2 receptor. In the search ofa potential interaction between neurotensin NTS2 receptor andnitric oxide synthase (NOS), levocabastine was administered to ratsand NOS activity was evaluated in cerebral cortex synaptosomalmembranes. Taken into account the relationship betweencatecholaminergic and neurotensinergic systems and the action ofcatecholamines on the activity of NOS, it was of interest to studythe potential relationship between NTS2 receptor and 3Hnoradrenalineuptake by hypothalamus slices. Levocabastine (50μg/kg, i.p., 30 min) or vehicle (saline solution) was administered tomale Wistar rats. One group of rats was employed to obtain cerebral cortex synaptosomal membranes by differential and gradientcentrifugation for evaluation of NOS activity. In another group ofanimals, anterior and posterior hypothalamic sections were processedfor the assay of 3H-noradrenaline uptake. NOS activity insynaptosomal membranes was decreased roughly by 50% both bylevocabastine administration or by in vitro addition of 10-5Mlevocabastine. Concomitantly, levocabastine administrationenhanced 3H-noradrenaline uptake by 35% and 12% in anterior andposterior hypothalamus, respectively. Results suggested an interrelationship between NTS2 receptor, NO synthesis andnoradrenaline levels at central nervous system.