Inhibition of rat synaptic membrane Na+/K+-ATPase and ecto-nucleoside triphosphate diphosphohydrolases by 12-tungstosilicic and 12-tungstophosphoric acid
АуториČolović, Mirjana B.
Bajuk-Bogdanović, Danica V.
Holclajtner-Antunović, Ivanka D.
Bosnjakovic-Pavlovic, Nada S.
Vasić, Vesna M.
Krstić, Danijela Z.
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C. The in vitro influence of Keggin structure polyoxotungstates, 12-tungstosilicic acid, H4SiW12O40 (WSiA) and 12-tungstophosphoric acid, H3PW12O40 (WPA), and monomer Na2WO4 x 2H(2)O on rat synaptic plasma membrane (SPM) Na+/K+-ATPase and E-NTPDase activity was studied, whereas the commercial porcine cerebral cortex Na+/K+-ATPase served as a reference. Dose-dependent Na+/K+-ATPase inhibition was obtained for all investigated compounds. Calculated IC50 (10 min) values, in mol/l, for SPM/commercial Na+/K+-ATPase, were: 3.4 x 10(-6)/4.3 x 10(-6), 2.9 x 10(-6)/3.1 x 10(-6) and 1.3 x 10(-3)/1.5 x 10(-3) for WSiA, WPA and Na2WO4 x 2H(2)O, respectively. In the case of E-NTPDase, increasing concentrations of WSiA and WPA induced its activity reduction, while Na2WO4 x 2H(2)O did not noticeably affect the enzyme activity at all investigated concentrations (up to 1 x 10(-3) mol/l). IC50 (10 min) values, obtained from the inhibition curves, were (in mol/l): 4.1 x 10(-6) for WSiA and 1.6 x 10(-6) f...or WPA. Monolacunary Keggin anion was found as the main active molecular species present under physiological conditions (in the enzyme assays, pH 7.4), for the both polyoxotungstates solutions (1 mmol/l), using Fourier transform infrared (FT-IR) and micro-Raman spectroscopy. Additionally, commercial porcine cerebral cortex Na+/K+-ATPase was exposed to the mixture of Na2WO4 x 2H(2)O and WSiA at different concentrations. Additive inhibition effect was achieved for lower concentrations of Na2WO4 x 2H(2)O/WSiA ( LT = 1 x 10(-3)/ 4 x 10(-6) mol/l), while antagonistic effect was obtained for all higher concentrations of the inhibitors. (C) 2011 Elsevier Ltd. All rights reserved.
Кључне речи:12-Tungstosilicic acid / 12-Tungstophosphoric acid / Monolacunary Keggin anion / Na2WO4 x 2H(2)O / Na+/K+-ATPase / Ecto-nucleoside triphosphate diphosphohydrolases / Simultaneous exposure
Извор:Bioorganic and Medicinal Chemistry, 2011, 19, 23, 7063-7069
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ISSN: 0968-0896 (print)