NDLI: The Administration of Levocabastine, a NTS2 Receptor Antagonist, Modifies Na$^{+}$, K$^{+}$-ATPase Properties

Content Provider	Springer Nature Link
Author	Gutnisky, Alicia López Ordieres, María Graciela Rodríguez de Lores Arnaiz, Georgina
Copyright Year	2016
Abstract	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 [$^{3}$H]-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 [$^{3}$H]-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.
Starting Page	1274
Ending Page	1280
Page Count	7
File Format	PDF
ISSN	03643190
Journal	Neurochemical Research
Volume Number	41
Issue Number	6
e-ISSN	15736903
Language	English
Publisher	Springer US
Publisher Date	2016-01-07
Publisher Place	New York
Access Restriction	One Nation One Subscription (ONOS)
Subject Keyword	Central nervous system membranes Synaptosomal membranes Cerebral cortex Na$^{+}$ K$^{+}$-ATPase K$^{+}$-p-Nitrophenylphosphatase Neurotensin [$^{3}$H]-Ouabain binding Levocabastine NTS1 Receptor NTS2 Receptor Neurosciences Neurochemistry Biochemistry Cell Biology Neurology
Content Type	Text
Resource Type	Article
Subject	Medicine Biochemistry Cellular and Molecular Neuroscience

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