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Neurotensin inhibits neuronal Na+,K+-ATPase activity through high affinity peptide receptor
M G López Ordieres1, G Rodríguez de Lores Arnaiz
1Instituto de Biología Celular y Neurociencias Prof. Eduardo De Robertis, Facultad de Medicina, PROBICENE-CONICET and Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Paraguay 2155, 1121, Buenos Aires, Argentina.
Abstract:
Neurotensin is a peptide present in mammalian CNS and peripheral tissues, which may play a major role in neurotransmission or neuromodulation, subserving diverse physiological functions. We studied the effect of added neurotensin on ATPase activities in synaptosomal membranes isolated from rat cerebral cortex. Neurotensin at 3 x 10(-8)-3 x 10(-6) M concentration decreased 20-44% Na+,K+-ATPase activity but failed to modify Mg2+-ATPase activity; lower neurotensin concentrations (3 x 10(-14)-3 x 10(-10) M) had no effect on enzyme activities. This inhibitory effect was abolished by neurotensin heating, by enzyme preincubation with neurotensin during periods exceeding 10 min, or by adding 1 x 10(-6) M SR 48692, a high affinity neurotensin receptor antagonist. Levocabastine, which blocks low affinity neurotensin receptor, failed to alter enzyme inhibition by the peptide. It is suggested that the sodium pump may be a target for neurotensin effects at neuronal level involving the participation of high affinity neurotensin receptor.