title: Inhibition of mammal Na(+)K(+)-ATPase by diterpenes extracted from the Brazilian brown alga Dictyota cervicornis.
abstract: The dolastane diterpenes 4-acetoxy-9,14-dihydroxydolast-1(15),7-diene (1) and 4,7-diacetoxy-14-hydroxydolast-1(15),8-diene (2) were isolated from specimens of the alga Dictyota cervicornis collected from the Rio de Janeiro coast, Brazil. Chemical structures of the diterpenes were assigned by 1D and 2D NMR spectral data for the first time. Both substances inhibited Na(+)K(+)-ATPase preparations from guinea-pig brain or kidney, with the same inhibitory potency towards enzyme isoforms. The maximal inhibition obtained for 1 was 40% at a concentration of 0.5 mm in the incubation mixture, while it reached 80% for compound 2 at this concentration. Ouabain insensitive ATPases were inhibited by 1, but not by 2. Data comparing the inhibitory potency of these compounds with that of ouabain and oleic acid suggest a higher degree of selectivity of 2 towards the Na(+)K(+)-pump. Cardiac glycosides such as ouabain are used classically in the treatment of heart failure, but alterations of Na(+)K(+)-pump activity are also involved in several other diseases. Therefore, the study of compounds interfering with this pump activity is gaining further importance.
authors.affiliation: Departamento de Biologia Celular e Molecular, Instituto de Biologia, Universidade Federal Fluminense, Niterói, RJ, Brazil.
authors.forename: Diogo Gomes
authors.initials: DG
authors.lastname: Garcia
authors.forename: Everson Miguel
authors.initials: EM
authors.lastname: Bianco
authors.forename: Maria da Conceição Batista Dos
authors.initials: Mda C
authors.lastname: Santos
authors.forename: Renato Crespo
authors.initials: RC
authors.lastname: Pereira
authors.forename: Mauro Velho de Castro
authors.initials: MV
authors.lastname: Faria
authors.forename: Valeria Laneuville
authors.initials: VL
authors.lastname: Teixeira
authors.forename: Patrícia
authors.initials: P
authors.lastname: Burth
mesh_terms: D000818:Animals; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D004791:Enzyme Inhibitors / Q000302:isolation & purification / Q000494:pharmacology*; D006168:Guinea Pigs; D015394:Molecular Structure; D000459:Phaeophyceae / Q000737:chemistry*; D000254:Sodium-Potassium-Exchanging ATPase / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: C542296:4,7-diacetoxy-14-hydroxydolast-1(15),8-diene; C542295:4-acetoxy-9,14-dihydroxydolast-1(15),7-diene; D004224:Diterpenes; D004791:Enzyme Inhibitors; D000254:Sodium-Potassium-Exchanging ATPase