title: Insights into the mechanism of Na+,K+-ATPase inhibition by 2-methoxy-3,8,9-trihydroxy coumestan.
abstract: The molecular mechanisms involved in Na+,K+-ATPase inhibition by 2-methoxy-3,8,9-trihydroxy coumestan were investigated. We show that this compound decreases the free sulfydryl groups present in the enzyme and that its inhibitory effect is prevented by dithiothreitol and other two sulfydryl containing reagents. We propose a redox cycle culminating with the irreversible oxidation of sulfydryl groups essential for the catalytic activity of this enzyme and of two other related P-type ATPases.
authors.affiliation: Departamento de Farmacologia Básica e Clínica, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, RJ 21941-590, Brazil.
authors.forename: Elisa S C
authors.initials: ES
authors.lastname: Pôças
authors.forename: Natália A
authors.initials: NA
authors.lastname: Touza
authors.forename: Paulo H C
authors.initials: PH
authors.lastname: Pimenta
authors.forename: Fernanda B
authors.initials: FB
authors.lastname: Leitão
authors.forename: Chaquip D
authors.initials: CD
authors.lastname: Neto
authors.forename: Alcides J M
authors.initials: AJ
authors.lastname: da Silva
authors.forename: Paulo R R
authors.initials: PR
authors.lastname: Costa
authors.forename: François
authors.initials: F
authors.lastname: Noël
mesh_terms: D000818:Animals; D000925:Anticoagulants / Q000494:pharmacology*; D017301:Ca(2+) Mg(2+)-ATPase / Q000037:antagonists & inhibitors / Q000378:metabolism; D020134:Catalytic Domain; D003374:Coumarins / Q000494:pharmacology*; D004229:Dithiothreitol / Q000737:chemistry / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D017506:H(+)-K(+)-Exchanging ATPase / Q000378:metabolism; D007529:Isoflavones / Q000494:pharmacology*; D007668:Kidney / Q000187:drug effects* / Q000201:enzymology; D010084:Oxidation-Reduction; D054328:Proton Pump Inhibitors; D051381:Rats; D017208:Rats, Wistar; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000378:metabolism; D013438:Sulfhydryl Compounds / Q000737:chemistry / Q000378:metabolism
chemical_list: C495408:2-methoxy-3,8,9-trihydroxy coumestan; D000925:Anticoagulants; D003374:Coumarins; D004791:Enzyme Inhibitors; D007529:Isoflavones; D054328:Proton Pump Inhibitors; D013438:Sulfhydryl Compounds; D017301:Ca(2+) Mg(2+)-ATPase; D017506:H(+)-K(+)-Exchanging ATPase; D000254:Sodium-Potassium-Exchanging ATPase; C505898:coumestan; D004229:Dithiothreitol