title: Inhibition of rat synaptic membrane Na⁺/K⁺-ATPase and ecto-nucleoside triphosphate diphosphohydrolases by 12-tungstosilicic and 12-tungstophosphoric acid.
abstract: The in vitro influence of Keggin structure polyoxotungstates, 12-tungstosilicic acid, H(4)SiW(12)O(40) (WSiA) and 12-tungstophosphoric acid, H(3)PW(12)O(40) (WPA), and monomer Na(2)WO(4) × 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 IC(50) (10 min) values, in mol/l, for SPM/commercial Na(+)/K(+)-ATPase, were: 3.4 × 10(-6)/4.3 × 10(-6), 2.9 × 10(-6)/3.1 × 10(-6) and 1.3 × 10(-3)/1.5 × 10(-3) for WSiA, WPA and Na(2)WO(4) × 2H(2)O, respectively. In the case of E-NTPDase, increasing concentrations of WSiA and WPA induced its activity reduction, while Na(2)WO(4) × 2H(2)O did not noticeably affect the enzyme activity at all investigated concentrations (up to 1 × 10(-3)mol/l). IC(50) (10 min) values, obtained from the inhibition curves, were (in mol/l): 4.1 × 10(-6) for WSiA and 1.6 × 10(-6) for 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 Na(2)WO(4) × 2H(2)O and WSiA at different concentrations. Additive inhibition effect was achieved for lower concentrations of Na(2)WO(4) × 2H(2)O/WSiA (≤ 1 × 10(-3)/4 × 10(-6) mol/l), while antagonistic effect was obtained for all higher concentrations of the inhibitors.
authors: Department of Physical Chemistry, Vinča Institute of Nuclear Sciences, University of Belgrade, M. Petrović 12-14, PO Box 522, 11001 Belgrade, Serbia. colovicm@vinca.rs
authors: Mirjana B
authors: MB
authors: Čolović
authors: Danica V
authors: DV
authors: Bajuk-Bogdanović
authors: Nataša S
authors: NS
authors: Avramović
authors: Ivanka D
authors: ID
authors: Holclajtner-Antunović
authors: Nada S
authors: NS
authors: Bošnjaković-Pavlović
authors: Vesna M
authors: VM
authors: Vasić
authors: Danijela Z
authors: DZ
authors: Krstić
mesh_terms: D000818:Animals; D015703:Antigens, CD / Q000378:metabolism; D001081:Apyrase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D008297:Male; D008958:Models, Molecular; D010756:Phosphoric Acids / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D012824:Silicic Acid / Q000494:pharmacology*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D017550:Spectroscopy, Fourier Transform Infrared; D013059:Spectrum Analysis, Raman; D013570:Synaptic Membranes / Q000187:drug effects* / Q000201:enzymology*; D017973:Tungsten Compounds / Q000494:pharmacology*
chemical_list: C519880:12-tungstophosphoric acid; D015703:Antigens, CD; D004791:Enzyme Inhibitors; D010756:Phosphoric Acids; D017973:Tungsten Compounds; D012824:Silicic Acid; D001081:Apyrase; C067869:CD39 antigen; D000254:Sodium-Potassium-Exchanging ATPase