[3H]-OUABAIN AND [3H]-NEUROTENSIN BINDING TO RAT STRIATAL MEMBRANES IS MODIFIED BY ADMINISTRATION OF ANTIPSYCHOTICS HALOPERIDOL AND CLOZAPINE.

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

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

Nova Science Publishers, Inc.

Lugar: Nueva York ; Año: 2021; p. 77 - 100

Previous work indicates that peptide neurotensin inhibits synaptosomal membrane Na+, K+-ATPase activity. Anatomical and biochemical evidences indicate a relationship between neurotensinergic and dopaminergic systems and that both systems are involved in the action mechanism of antipsychotic drugs. Haloperidol and clozapine are antipsychotic drugs currently employed in therapeutics. They are prototypes for typical and atypical antipsychotic drugs, respectively. The objective of the work was to analyze potential relationships between neuronal Na+, K+-ATPase with neurotensinergic and dopaminergic systems. After the blockade of dopaminergic receptors, an alteration of Na+, K+-ATPase properties and neurotensin binding to rat cerebral cortex membranes was recorded. Herein, the study was extended to rat striatum. Haloperidol (2 mg/kg) and clozapine (10 mg/kg) were administered i.p. to rats and 18 hours later, animals were sacrificed, striatum harvested, membrane fractions prepared and high affinity [3H]-ouabain binding assayed. Basal high affinity [3H]-ouabain binding remained unchanged after haloperidol administration whereas it decreased (- 50%) after clozapine administration. With respect to basal values neurotensin addition (10 micromolar concentration) decreased (- 50%) [3H]-ouabain binding after haloperidol administration whereas it enhanced (+ 100%) binding after clozapine administration. Saturation curves for [3H]-neurotensin binding followed by Scatchard and Hill analysis showed that peptide binding affinity (Bmax value) decreased roughly 70% after clozapine administration but remained unaltered after haloperidol administration. Kd and NH values remained unaltered in all cases. Results indicated that typical and atypical antipsychotic drugs differentially modify Na+, K+-ATPase ouabain site (K+ site) and NTS1 neurotensin receptor at striatum. At the same time, support the notion of an interaction between dopaminergic and neurotensinergic systems and Na+, K+-ATPase at central synapses.