THE INHIBITORY EFFECT OF NEUROTENSIN ON NEURONAL Na+ K+- ATPase ACTIVITY IS ALTERED BY CLOZAPINE.

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

Madison, Wisconsin, EE.UU.

Congreso; XXXVI Congreso de la Sociedad Americana de Neuroquímica (ASN); 2005

Sociedad Americana de Neuroquímica (ASN)

The inhibitory effect of neurotensin on neuronal Na+  K+- ATPase activity is altered by clozapine. G. Rodríguez de Lores Arnaiz and M. G. López Ordieres. Cátedra de Farmacología, Facultad  Farmacia y Bioquímica. Instituto de Biología Celular y Neurociencias "Prof. E. De Robertis". Facultad de Medicina, Universidad de Buenos Aires. Paraguay 2155. Buenos Aires. Argentina. E mail: grodrig@ffyb.uba.ar   Neurotensin acts as a neurotransmitter or a neuromodulator in the mmamalian brain. It has been reported that a single dose of the atypical antipsychotic clozapine (10 mg/ kg) increases neurotensin levels in some CNS areas without affecting those in prefrontal cortex or striatum. We have previously demonstrated that neurotensin inhibits neuronal Na+, K+-ATPase activity through high affinity peptide receptor (NTS1), an effect totally prevented by acute treatment with the typical antipsychotic haloperidol. The study was extended to analyze potential clozapine effect on Na+, K+-ATPase inhibition by neurotensin. The drug was administered to rats (10mg/kg) and animals were decapited 18 hs later. Cerebral cortex and striatum were removed and subjected to differential and sucrose gradient centrifugation to obtain synaptosomal membrane fractions. Na+, K+-ATPase activity in the presence 3.5 x 10-6 M neurotensin decreased 44 % and 30% in control cortical and striatal membranes, respectively. After clozapine administration neurotensin produced respectively 26% increase but 25% decrease in cortical and striatal membrane Na+, K+-ATPase activity. In vitro addition of 1.0 x 10-6 M clozapine failed to modify synaptosomal membrane enzyme inhibition by 3.5 x 10-6 M neurotensin. These findings show that neurotensin effect on neuronal Na+, K+- ATPase activity differs according to the antipsychotic administered. These results provide an alternative explanation to the characteristics adverse effects recorded for atypical versus typical antipsychotic agents.