ALTERATION OF SODIUM-POTASSIUM-ADENOSINE TRIPHOSPHATASE RESPONSE TO NEUROTENSIN IN A DIABETIC STAGE

G. RODRÍGUEZ DE LORES ARNAIZ ; C. ROSIN; J. MIÑO ; M. G. LÓPEZ ORDIERES

Long Beach, California

Congreso; XXXXV Congreso de la Sociedad Americana de Neuroquímica (ASN); 2014

ASN

Alteration of sodium-potassium-adenosine triphosphatase response to neurotensin in a diabetic stage. Georgina Rodríguez de Lores Arnaiz1, Carina Rosin1,2, Jorge Miño2, María Graciela López Ordieres1,2 1Instituto de Biología Celular y Neurociencias Prof. E. De Robertis, Facultad de Medicina and 2Cátedra de Farmacología, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Paraguay 2155, 1121-Buenos Aires, Argentina. E-mail: grodrig@ffyb.uba.ar Neurotensin is a tridecapeptide which can act as a neuromodulator or a neurotransmitter, and binds to a group of receptors. Neurotensin is able to inhibit Na/K-ATPase activity, an effect blocked by the presence of antagonist SR48692, suggesting the involvement of high affinity neurotensin (NTS1) receptor. Evidences suggest a relationship between neurotensinergic system and glycemia levels. Potential Na/K-ATPase activity regulation by neurotensin in cerebral cortex synaptosomal membranes obtained from rats turned hyperglycaemic was explored. To produce diabetes mellitus rats were administered with Streptozotocin (STZ), a specific toxic to the pancreatic beta cells. Animals received a single i.p. STZ injection at a dose of 60 mg/kg dissolved in 0.01 M citrate buffer, pH 4.5 (vehicle). To serve as controls, rats injected with the vehicle were processed. Synaptosomal membranes from rat cerebral cortex were isolated by differential centrifugation and sucrose gradient. In membrane samples Na/K-ATPase activity was measured in the absence or presence of neurotensin solution by colorimetric determination of inorganic phosphate released. 3H-neurotensin binding and Western blot analysis for Na/K-ATPase alpha 3 subunit were carried out in cerebral cortex crude membrane preparations. Neurotensin inhibited Na/K-ATPase activity in a dose-dependent manner in control synaptosomal membranes. In synaptosomal membranes isolated from diabetic rats the peptide failed to modify Na/K-ATPase activity (at 10-8 - 10-7M concentration) or slightly enhanced the enzyme activity (at 10-6M concentration). STZ treatment decreased the affinity of NTS1 receptor for neurotensin and the expression of Na/K-ATPase alpha 3 isoform in cerebral cortex. It was concluded that STZ administration alters the response of Na/K-ATPase to neurotensin, an effect which seems to involve a decrease in enzyme alpha 3 isoform expression and NTS1 receptor affinity for the peptide.