CLOZAPINE ACUTE ADMINISTRATION DOSE DEPENDENTLY MODIFIES NEUROTENSIN EFFECT ON Na/K-ATPase ACTIVITY.

M. G. LÓPEZ ORDIERES; G. RODRÍGUEZ DE LORES ARNAIZ

Innsbruck, Austria

Congreso; XX Congreso de la Sociedad Internacional de Neuroquímica (ISN); 2005

Sociedad Internacional de Neuroquímica (ISN)

NEUROTENSIN EFFECT ON CENTRAL MUSCARINIC RECEPTORS IS INDEPENDENT OF HIGH AFFINITY NEUROTENSIN RECEPTOR (NTS1). Schneider, P.G., López Ordieres, M.G., Okita Kokubu B.A., Magliarella P. and Rodríguez de Lores Arnaiz, G. Instituto de Biología Celular y Neurociencias “Prof. E. De Robertis”. Facultad de Medicina. Universidad de Buenos Aires. Paraguay 2155. (1121) Buenos Aires. Argentina. e-mail: patriciaschneider@fibertel.com.ar Neurotensin (NT) is a tridecapeptide distributed in central and peripheral nervous system, which can behave as a neurotransmitter or neuromodulator of dopaminergic and cholinergic transmission. Previous studies demonstrated that NT is able to inhibit the activity of synaptosomal membrane Na+, K+-ATPase and to decrease the binding of tritiated quinuclidinyl benzilate ([3H]-QNB) to rat cerebral cortex, hippocampal and cerebellar  membranes. NT action on the enzyme was blocked with SR 48692, a specific antagonist for high affinity NT receptor (NTS1). The purpose of this study was to evaluate the potential participation of NTS1 receptor in the inhibition of [3H]-QNB binding by NT. Rat cerebral cortex, cerebellar and hippocampal membranes were incubated with SR 48692 10-6­ M dissolved in dimethylsulfoxide (DMSO) 10% v/v in the presence or absence of NT 10-6­­ M. As controls, membranes were incubated with DMSO and/or NT 10-6 M plus DMSO. It was observed that NT+DMSO decreased 49%, 32% and 53% [3H]-QNB binding to cerebral cortex, cerebellar and hippocampal membranes, respectively; this inhibition was not observed by the single presence of DMSO. Membranes preincubated with SR 48692 10-6 M did not alter NT effect on binding. SR 48692 10-6 M decreased 50% the binding only to cerebral cortex membranes, suggesting a possible direct effect on muscarinic receptors in this area. These results indicate that in ligand binding inhibition to muscarinic receptor by NT, high affinity NT receptor is not involved.