The administration of levocabastine, a NTS2 receptor antagonist, modifies Na+, K+-ATPase properties
| Autor: | Alicia Gutnisky, Georgina Rodríguez de Lores Arnaiz, María Graciela López Ordieres |
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| Jazyk: | angličtina |
| Rok vydání: | 2016 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty NTS2 receptor CIENCIAS MÉDICAS Y DE LA SALUD medicine.drug_class Neurociencias Biochemistry 03 medical and health sciences Cellular and Molecular Neuroscience chemistry.chemical_compound 0302 clinical medicine Piperidines Internal medicine medicine Animals Receptors Neurotensin Na+/K+-ATPase Rats Wistar Neurotransmitter Receptor Ouabain Synaptosomal membranes Levocabastine K+-p-Nitrophenylphosphatase Neurotensin Cerebral Cortex K+-ATPase Antagonist NTS1 receptor General Medicine Na+ Cerebral cortex Receptor antagonist Rats Medicina Básica 030104 developmental biology Endocrinology Membrane chemistry Central nervous system membranes Sodium-Potassium-Exchanging ATPase [3H]-Ouabain binding 030217 neurology & neurosurgery medicine.drug Protein Binding |
| DOI: | 10.1007/s11064-015-1823-7 |
| Popis: | 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). The administration of levocabastine (antagonist for NTS2 receptor) does not prevent Na+, K+-ATPase inhibition by neurotensin when the enzyme is assayed with ATP as substrate. Herein levocabastine effect on Na+, K+-ATPase K+ site was explored. For this purpose, levocabastine was administered to rats and K+-p-nitrophenylphosphatase (K+-p-NPPase) activity in synaptosomal membranes and [3H]-ouabain binding to cerebral cortex membranes were assayed in the absence (basal) and in the presence of neurotensin. Male Wistar rats were administered with levocabastine (50 μg/kg, i.p., 30 min) or the vehicle (saline solution). Synaptosomal membranes were obtained from cerebral cortex by differential and gradient centrifugation. The activity of K+-p-NPPase was determined in media laking or containing ATP plus NaCl. In such phosphorylating condition enzyme behaviour resembles that observed when ATP hydrolyses is recorded. In the absence of ATP plus NaCl, K+-p-NPPase activity was similar for levocabastine or vehicle injected (roughly 11 μmole hydrolyzed substrate per mg protein per hour). Such value remained unaltered by the presence of 3.5 × 10−6 M neurotensin. In the phosphorylating medium, neurotensin decreased (32 %) the enzyme activity in membranes obtained from rats injected with the vehicle but failed to alter those obtained from rats injected with levocabastine. Levocabastine administration enhanced (50 %) basal [3H]-ouabain binding to cerebral cortex membranes but failed to modify neurotensin inhibitory effect on this ligand binding. It is concluded that NTS2 receptor blockade modifies the properties of neuronal Na+, K+-ATPase and that neurotensin effect on Na+, K+-ATPase involves NTS1 receptor and -at least partially- NTS2 receptor. Fil: Gutnisky, Alicia. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina Fil: López Ordieres, María Graciela. Universidad de Buenos Aires. Facultad de Farmacia y Bioquímica. Departamento de Farmacología. Cátedra de Farmacología; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina Fil: Rodriguez, Georgina Emma. Consejo Nacional de Investigaciones Científicas y Técnicas. Oficina de Coordinación Administrativa Houssay. Instituto de Biología Celular y Neurociencia "Prof. Eduardo de Robertis". Universidad de Buenos Aires. Facultad de Medicina. Instituto de Biología Celular y Neurociencia; Argentina |
| Databáze: | OpenAIRE |
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