Postnatal Nitric Oxide Inhibition Modifies Neurotensin Effect on ATPase Activity

Abstract

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. Assays were carried out at two stages: juvenile (35 days) and adult (56 days) ages. In an open field task, results recorded in juvenile rats markedly differed from those obtained in adult rats. The presence of neurotensin at 3.5 × 10(-8)-3.5 × 10(-6 )M concentration decreased 16-34% Na(+), K(+)-ATPase activity in membranes purified from control animals. At variance, the peptide failed to alter this enzyme activity in membranes obtained after L-NAME treatment. After administration of L-NAME, [(3)H]-ouabain binding to membranes isolated from adult male rats decreased 64% in the presence of 1.0 × 10(-6 )M neurotensin, a peptide concentration which only slightly decreased binding to membranes isolated from juvenile rats. It is postulated that early postnatal NO dysfunction may exert a permanent change in neurotensin system that influence later Na(+), K(+)-ATPase response to neurotensin.

The low affinity neurotensin receptor antagonist levocabastine impairs brain nitric oxide synthesis and mitochondrial function by independent mechanisms

“…The inhibitory effect of neurotensin on Na + , K + ‐ATPase activity is impaired by neonatal treatment to rats with Nω‐nitro‐ l ‐arginine methyl ester hydrochloride, which blocks the synthesis of NO (López Ordieres et al . ).…”