IBCN   20355
INSTITUTO DE BIOLOGIA CELULAR Y NEUROCIENCIA "PROFESOR EDUARDO DE ROBERTIS"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
SOMATOSTATIN AND VAPREOTIDE EFFECTS ON CORTICAL ATPase ACTIVITY
Autor/es:
M. G. LÓPEZ ORDIERES; D. CAMPO; C. UMPÌERRE; A. KEMMLING ; G. RODRÍGUEZ DE LORES ARNAIZ
Lugar:
Rosario, Pcia. de Santa Fe
Reunión:
Congreso; II Reunión Internacional de Ciencias Farmacéuticas (RICIFA); 2012
Institución organizadora:
Universidad de Rosario
Resumen:
Introduction Somatostatin (sst) was first identified as a hypothalamus factor that inhibits the release of growth hormone from the anterior pituitary (1, 2). Both somatostatin and its receptors were subsequently found widely distributed within and outside the nervous system. Reflecting this wide distribution, somatostatin has been implicated regulating a diverse array of biological processes. These include body growth, homeostasis, sensory perception, autonomous functions, rate of intestinal absorption, behaviour, including cognition and memory, and developmental processes. Somatostatin receptors are distinguished by their affinities for somatostatin analogues, for example, vapreotide is an analogue which behaves as agonist of sst1, sst2 and sst5 receptors (3). The main active transport system in neurons, as in most other animal cells, is the sodium pump or Na+, K+-ATPase that extrudes 3 Na+ and accumulates 2 K+ per molecule of ATP hydrolyzed. It is responsible to establish and maintain the electrochemical gradient, essential for synaptic transmission (4). Plasma membrane Ca2+ -ATPase serves to remove calcium from the cell; it is vital for regulating the amount of calcium within the cells (5) There is a transmembrane electrochemical gradient of Ca2+ driving the entry of the ion into the cells, which is very important for cells to maintain low concentrations of Ca2+ for a proper cell signalling. As ATPase activity may be modified by different substances, such as catecholamines and neuropeptides (6-9). Therefore, the purpose of this work was to investigate the effect of somatostatin and its analogue, vapreotide on ATPase activity in membranes obtained from the cerebral cortex. Materials and methods -          Male Sprague- Dawley rats maintained in a 12-h light: dark cycle and with access to food and water ad libitum were employed. -          Ouabain, disodium ATP (grade I, prepared by phosphorylation of adenosine), somatostatin, vapreotide and ATPase from pig cerebral cortex were from Sigma Chemical Co. (St. Louis, MO, USA). -          Synaptosomal membranes were isolated by differential and sucrose gradient centrifugation as previously described in this laboratory (10). -          ATPase activity was measured as described Albers et al. (11). -          [3H]-ouabain binding assays were carried as described by Antonelli et al. (12). Results -          The presence of 1.0 x 10-9- 1.0 x 10-6 M vapreotide produced Na+, K+-ATPase inhibition with a IC50 = 7.87 x10-7 M, but this peptide concentration range failed to modify Ca2+-ATPase and Mg2+-ATPase activities in cortical synaptosomal membranes. -          Rats administered with vapreotide (100 μg/kg, i.p.) produced  25% stimulation of Na+, K+-ATPase activity, a slight reduction of Mg2+-ATPase activity and no modification of  Ca2+-ATPase activity. -          The presence of 1.0 x 10-9- 1.0 x 10-5 M somatostatin produced no changes in cortical Na+, K+-ATPase, but 1.0 x 10-6 M somatostatin decreased 16% [3H]-ouabain specific binding in membranes. -          In pig cerebral cortex, Na+, K+-ATPase activity diminished  28% by the addition of 1.0 x 10-6 M vapreotide to the incubation media in the assay for ATPases whereas at the same concentration, somatostatin produced a 35% stimulation of this activity. Conclusions Results presented suggest a different behaviour between somatostatin and its analogue peptide, vapreotide in relation to cerebral ATPase activities possibly due to characteristic interactions among them. Acknowledgments Financial support was provided by CONICET and Universidad de Buenos Aires, Argentina. References (1)      Brazeau P, Vale W, Burgus R, Ling N, Butcher  M, Rivier J, Guillemin R. Hypothalamic polypeptide that inhibits the secretion of immunoreactive pituitary growth hormone. Science 1973; 179:77-79. (2)      Epelbaum, J. Somatostatin in the central nervous system: Physiology and pathological modifications. Progress in Neurobiology 1986; 27:63-100. (3)      Bruns C, Weckbecker G, Raulf F, Lübbert H, Hoyer D. Characterization of somatostatin receptor subtypes. Ciba Found Symp. 1995; 190:89-101. (4)      Rodríguez de Lores Arnaiz G. Na+, K+- ATPase in the brain: structure and function. En Neural Membranes and Transport (Ed. M. E. A. 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