ALTERATION OF NEUROTENSIN BINDING TO CEREBRAL CORTEX MEMBRANES BY ANTIPSYCHOTIC AGENTS

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

Córdoba

Congreso; XXXVIII Reunión Anual de la Asociación Argentina de Farmacología Experimental (SAFE); 2006

Asociación Argentina de Farmacología Experimental (SAFE)

Synaptosomal membrane Na+, K +-ATPase is inhibited by neurotensin (NT), an effect which involves high affinity neurotensin receptor (NTS1). In previous work,  we studied NT effect on this enzyme activity of rats pretreated with antipsychotic agents. NT inhibitory effect on Na+, K +-ATPase activity was totally prevented with haloperidol whereas it was inverted after clozapine administration. In order to test whether these effects were related to alteration of peptide binding to its receptor, herein [3H]-NT binding to cortical membranes after i.p administration of haloperidol (2 mg/kg) and clozapine (10 mg/kg) was analyzed. Rat cerebral cortex was removed and subjected to differential centrifugation in the presence of Tris-HCl buffer (pH=7.5) to obtain membrane fractions. It was observed that specific ligand binding increased to 198 ± 24% (n=3) whereas it decreased to 67.5 ± 9 (n= 4)  with respect to control membranes after administration of haloperidol and clozapine, respectively. These changes in NT binding are not attributable to Na+, K +-ATPase alteration since basal enzyme activity (31 to 33  mmoles. mg  prot-1. min-1) remained unaltered by haloperidol or clozapine treatments. It is postulated that opposite response of Na+, K +-ATPase to NT after antipsychotic administration may be due to alteration of peptide binding to its receptor. Presentación poster.