Changes in [H]-ouabain and [H]-neurotensin binding to rat cerebral cortex membranes after administration of antipsychotic drugs haloperidol and clozapine.

Evidences indicate the relationship between neurotensinergic and dopaminergic systems. Neurotensin inhibits synaptosomal membrane Na, K-ATPase activity, an effect blocked by SR 48692, antagonist for high affinity neurotensin receptor (NTS1) type. Assays of high affinity [H]-ouabain binding (to analyze K site of Na, K-ATPase) show that in vitro addition of neurotensin decreases binding.

The Administration of Levocabastine, a NTS2 Receptor Antagonist, Modifies Na(+), K(+)-ATPase Properties.

Neurotensin behaves as a neuromodulator or as a neurotransmitter interacting with NTS1 and NTS2 receptors. Neurotensin in vitro inhibits synaptosomal membrane Na(+), K(+)-ATPase activity. This effect is prevented by administration of SR 48692 (antagonist for NTS1 receptor).

Brain Na(+), K(+)-ATPase Activity In Aging and Disease.

Na(+)/K(+) pump or sodium- and potassium-activated adenosine 5'-triphosphatase (Na(+), K(+)-ATPase), its enzymatic version, is a crucial protein responsible for the electrochemical gradient across the cell membranes. It is an ion transporter, which in addition to exchange cations, is the ligand for cardenolides. This enzyme regulates the entry of K(+) with the exit of Na(+) from cells, being the responsible for Na(+)/K(+) equilibrium maintenance through neuronal membranes.

Neurotensin decreases high affinity [3H]-ouabain binding to cerebral cortex membranes.

Previous work from this laboratory showed the ability of neurotensin to inhibit synaptosomal membrane Na(+), K(+)-ATPase activity, the effect being blocked by SR 48692, a non-peptidic antagonist for high affinity neurotensin receptor (NTS1) [López Ordieres and Rodríguez de Lores Arnaiz 2000; 2001]. To further study neurotensin interaction with Na(+), K(+)-ATPase, peptide effect on high affinity [(3)H]-ouabain binding was studied in cerebral cortex membranes. It was observed that neurotensin modified binding in a dose-dependent manner, leading to 80% decrease with 1 × 10(-4)M concentration.

Postnatal nitric oxide inhibition modifies neurotensin effect on ATPase activity.

We have previously showed that peptide neurotensin inhibits neuronal Na(+), K(+)-ATPase activity, an effect which involves high affinity neurotensin receptor. Nitric oxide (NO) acts as a neurotransmitter or as a neuromodulator when it is synthesized by neuronal nitric oxide synthase. Neurotensin effect on Na(+), K(+)-ATPase activity was evaluated in cortical synaptosomal membranes isolated from rats injected at 3, 4 and 5 postnatal days with saline (control) or N (ω)-nitro-L-arginine methyl esther (L-NAME), a nitric oxide synthase inhibitor.

Neurotensin effect on Na+, K+-ATPase is CNS area- and membrane-dependent and involves high affinity NT1 receptor.

We have previously shown that peptide neurotensin inhibits cerebral cortex synaptosomal membrane Na+, K+-ATPase, an effect fully prevented by blockade of neurotensin NT1 receptor by antagonist SR 48692. The work was extended to analyze neurotensin effect on Na+, K+-ATPase activity present in other synaptosomal membranes and in CNS myelin and mitochondrial fractions. Results indicated that, besides inhibiting cerebral cortex synaptosomal membrane Na+, K+-ATPase, neurotensin likewise decreased enzyme activity in homologous striatal membranes as well as in a commercial preparation obtained from porcine cerebral cortex.