Neurotensin inhibits neuronal Na+,K+-ATPase activity through high affinity peptide receptor.
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.
López Ordieres
M G
MG
Instituto 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.
Rodríguez de Lores Arnaiz
G
G
D000818:Animals; D002540:Cerebral Cortex / Q000201:enzymology / Q000648:ultrastructure; D006361:Heating; D066298:In Vitro Techniques; D007425:Intracellular Membranes / Q000201:enzymology; D008297:Male; D009496:Neurotensin / Q000494:pharmacology / Q000502:physiology*; D010880:Piperidines / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D018028:Receptors, Neurotensin / Q000378:metabolism / Q000502:physiology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors*; D013574:Synaptosomes / Q000201:enzymology
D010880:Piperidines; D018028:Receptors, Neurotensin; D009496:Neurotensin; D000254:Sodium-Potassium-Exchanging ATPase; C047340:levocabastine