title: Effects of diene valepotriates from Valeriana glechomifolia on Na+/K+-ATPase activity in the cortex and hippocampus of mice.
abstract: Diene valepotriates obtained from Valeriana glechomifolia present antidepressant-like activity, mediated by dopaminergic and noradrenergic neurotransmissions. Also, previous studies have shown inhibitory activity of diene valepotriates towards Na(+)/K(+)-ATPase from the rat brain in vitro. Nevertheless, in vivo studies regarding the action of diene valepotriates on this enzyme are still lacking. Considering that Na(+)/K(+)-ATPase cerebral activity is involved in depressive disorders, the aim of this study was to investigate the effects of acute (5 mg/kg, p. o.) and repeated (5 mg/kg, p. o., once a day for three days) diene valepotriate administration on Na(+)/K(+)-ATPase activity in the cortex and hippocampus of mice submitted or not submitted to the forced swimming test. In addition, the protein expression of Na(+)/K(+)-ATPase α1, α2, and α3 isoforms in the cortex of mice repeatedly treated with diene valepotriates (and submitted or not submitted to the forced swimming test) was investigated. Diene valepotriates significantly decreased mice immobility time in the forced swimming test when compared to the control group. Only the animals repeatedly treated with diene valepotriates presented increased Na(+)/K(+)-ATPase activity in the cerebral cortex, and the exposure to the forced swimming test counteracted the effects of the diene valepotriates. No alterations in the hippocampal Na(+)/K(+)-ATPase activity were observed. Repeated diene valepotriate administration increased the cortical content of the α2 isoform, but the α3 isoform protein expression was augmented only in mice repeatedly treated with diene valepotriates and forced to swim. Mice treated with the vehicle and submitted to the forced swimming test also presented an increase in the content of the α2 isoform, but no alterations in Na(+)/K(+)-ATPase activity. These results suggest that cortical Na(+)/K(+)-ATPase may represent a molecular target of the diene valepotriates in vivo and long-term regulatory mechanisms are involved in this effect. Also, the forced swimming test per se influences the protein expression of Na(+)/K(+)-ATPase isoforms and counteracts the effects of the diene valepotriates on cortical Na(+)/K(+)-ATPase.
authors.affiliation: Programa de Pós Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Liz G
authors.initials: LG
authors.lastname: Müller
authors.affiliation: Programa de Pós Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Luisa
authors.initials: L
authors.lastname: Salles
authors.affiliation: Laboratório de Farmacologia Bioquímica e Molecular, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Helena A
authors.initials: HA
authors.lastname: Lins
authors.affiliation: Laboratório de Farmacologia Bioquímica e Molecular, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Priscilla R O
authors.initials: PR
authors.lastname: Feijó
authors.affiliation: Faculdade de Engenharia, Departamento de Engenharia Química, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Eduardo
authors.initials: E
authors.lastname: Cassel
authors.affiliation: Faculdade de Engenharia, Departamento de Engenharia Química, Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Rubem
authors.initials: R
authors.lastname: Vargas
authors.affiliation: Programa de Pós Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Gilsane L
authors.initials: GL
authors.lastname: von Poser
authors.affiliation: Laboratório de Farmacologia Bioquímica e Molecular, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: François
authors.initials: F
authors.lastname: Noël
authors.affiliation: Laboratório de Farmacologia Bioquímica e Molecular, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Rio de Janeiro, Brazil.
authors.forename: Luis E M
authors.initials: LE
authors.lastname: Quintas
authors.affiliation: Programa de Pós Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Stela M K
authors.initials: SM
authors.lastname: Rates
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D002540:Cerebral Cortex / Q000187:drug effects / Q000378:metabolism; D006624:Hippocampus / Q000187:drug effects / Q000378:metabolism; D039823:Iridoids / Q000494:pharmacology* / Q000627:therapeutic use; D008297:Male; D051379:Mice; D009043:Motor Activity / Q000187:drug effects*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology* / Q000627:therapeutic use; D020033:Protein Isoforms; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D013315:Stress, Psychological / Q000188:drug therapy; D013550:Swimming; D014632:Valerian / Q000737:chemistry*
chemical_list: D000928:Antidepressive Agents; D039823:Iridoids; D010936:Plant Extracts; D020033:Protein Isoforms; C009643:valtrates (combination); D000254:Sodium-Potassium-Exchanging ATPase