Neurotensin inhibitory effect on [3H]-ouabain binding to striatal membranes is inverted by administration of clozapine

CARINA ROSIN; GEORGINA RODRÍGUEZ DE LORES ARNAIZ; VICTORIA WIES; MARIA GRACIELA LÓPEZ ORDIERES

Na+, K+-ATPase: Discovery, Functions and Regulation

Nova Science Publishers, Inc.

Año: 2021; p. 77 - 100

Previous work indicates that peptide neurotensin inhibitssynaptosomal membrane Na+/K+-ATPase activity. Anatomical andbiochemical evidence indicates a relationship between neurotensinergicand dopaminergic systems and that both systems are involved in theaction mechanism of antipsychotic drugs. Haloperidol and clozapine areantipsychotic drugs currently employed in therapeutics. They areprototypes for typical and atypical antipsychotic drugs, respectively. Theobjective of the work was to analyze potential relationships betweenneuronal Na+/K+-ATPase with neurotensinergic and dopaminergicsystems. After the blockade of dopaminergic receptors, an alteration ofNa+/K+-ATPase properties and neurotensin binding to rat cerebral cortexmembranes was recorded. Herein, the study was extended to rat striatum.Haloperidol (2 mg/kg) and clozapine (10 mg/kg) were administered i.e.,to rats and 18 hours later, animals were sacrificed, striatum harvested,membrane fractions prepared and high affinity [3H]-ouabain bindingassayed. Basal high affinity [3H]-ouabain binding remained unchangedafter haloperidol administration whereas it decreased (-50%) afterclozapine administration. With respect to basal values neurotensinaddition (10 micromolar concentration) decreased (-50%) [3H]-ouabainbinding after haloperidol administration whereas it enhanced (+100%)binding after clozapine administration. Saturation curves for [3H]-neurotensin binding followed by Scatchard and Hill analysis showed thatpeptide binding affinity (Bmax value) decreased roughly 70% afterclozapine administration but remained unaltered after haloperidoladministration. Kd and NH values remained unaltered in all cases.Results indicated that typical and atypical antipsychotic drugsdifferentially modify Na+/K+-ATPase ouabain site (K+site) and NTS1neurotensin receptor at striatum. At the same time, support the notion ofan interaction between dopaminergic and neurotensinergic systems andNa+/K+-ATPase at central synapses.