LA ADMINISTRACION DE CLOZAPINA ALTERA LA INHIBICION DE LA Na/K-ATPasa PRODUCIDA POR LA NEUROTENSINA.

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

Mar del Plata, Pcia. de Buenos Aires, Argentina

Congreso; Primer Congreso Conjunto de Sociedades Biomédicas SAIC – SAI – SAFE – SAN – SABiología – SABiofísica – SAF,; 2004

SAIC – SAI – SAFE – SAN – SABiología – SABiofísica – SAF

The inhibitory effect of neurotensin on synaptosomal Na, K- ATPase activity is altered by clozapine. M. G. López Ordieres; G. Rodríguez de Lores Arnaiz M. G. López Ordieres Cátedra de Farmacología, Facultad de Farmacia y Bioquímica and 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 is a tridecapeptide present in mammalian central nervous system and peripheral tissues, whose widespread distribution in cell bodies and nerve terminals in the brain suggests that it may play a major role in neurotransmission or neuromodulation, subserving diverse physiological CNS functions. In the brain, neurotensin acts as a neuromodulator, particularly of dopaminergic transmission in nigrostriatal and mesocorticolimbic systems, thus implying its involvement in dopamine-associated neurodegenerative and neuropsychiatric disorders. It has been reported that a single dose of  atypical antipsychotic drug, such as clozapine (10 mg/ kg) increases neurotensin levels mainly in nucleus accumbens without affecting neurotensin concentration in the prefrontal cortex or striatum. We have previously reported that neurotensin inhibits neuronal Na+, K+-ATPase activity through high affinity peptide receptor (NTS1) an effect totally prevented by acute treatment with haloperidol. The study was extended to analyze potential clozapine effect, an atypical antipsychotic drug on Na+, K+-ATPase inhibition by neurotensin. The study was extended to analyze potential clozapine effect, an atypical antipsychotic drug on Na+, K+-ATPase inhibition by neurotensin. The drug was administered to rats 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 cortical and striatal membranes, respectively. After clozapine administration neurotensin produced 26% increase in cortical but 25 % decrease in 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 in relation to the type of antipsychotic administered and these results support an  alternative explanation to the characteristics adverse effects that antipsychotics produce.