title: Uliginosin B, a Possible New Analgesic Drug, Acts by Modulating the Adenosinergic System.
abstract: Uliginosin B (ULI) is a natural acylphloroglucinol that has been proposed as a new molecular scaffold for developing analgesic and antidepressant drugs. Its effects seem to be due to its ability to increase monoamines in the synaptic cleft by inhibiting their neuronal uptake without binding to their respective transporters, but its exact mode of action is still unknown. Considering the importance of the purinergic system to pain transmission and its modulation by monoamines availability, the aim of this study was to investigate the involvement of adenosinergic signaling in antinociceptive effect of uliginosin B. The selective adenosine A1 receptor antagonist DPCPX and the selective A2A antagonist ZM 241385 prevented the effect of ULI in the hot-plate test in mice. Pretreatment with inhibitors of adenosine reuptake (dipyridamole) or adenosine deaminase (EHNA) did not affect the ULI effect. On the other hand, its effect was completely prevented by an inhibitor of ecto-5'-nucleotidase (AMPCP). This finding was confirmed ex vivo, whereby ULI treatment increased AMP and ATP hydrolysis in spinal cord and cerebral cortex synaptosomes, respectively. Altogether, these data indicate that activation of A1 and A2A receptors and the modulation of ecto-5'-nucleotidase activity contribute to the antinociceptive effect of ULI.
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, 90610-000 Porto Alegre, Brazil.
authors.forename: Eveline Dischkaln
authors.initials: ED
authors.lastname: Stolz
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, 90610-000 Porto Alegre, Brazil.
authors.forename: Paola Fontoura
authors.initials: PF
authors.lastname: da Costa
authors.affiliation: Laboratório de Farmacologia da Dor e Neuromodulação: Investigações Pré-Clínicas, Departamento de Farmacologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90046-900 Porto Alegre, Brazil.
authors.forename: Liciane Fernandes
authors.initials: LF
authors.lastname: Medeiros
authors.affiliation: Laboratório de Farmacologia da Dor e Neuromodulação: Investigações Pré-Clínicas, Departamento de Farmacologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90046-900 Porto Alegre, Brazil.
authors.forename: Andressa
authors.initials: A
authors.lastname: Souza
authors.affiliation: Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90035-003 Porto Alegre, Brazil.
authors.forename: Ana Maria Oliveira
authors.initials: AM
authors.lastname: Battastini
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, 90610-000 Porto Alegre, Brazil.
authors.forename: Gilsane Lino
authors.initials: GL
authors.lastname: von Poser
authors.affiliation: Laboratório de Neuroquímica e Psicofarmacologia, Faculdade de Biociências, Pontificia Universidade Católica do Rio Grande do Sul, 90619-900 Porto Alegre, Brazil.
authors.forename: Carla
authors.initials: C
authors.lastname: Bonan
authors.affiliation: Laboratório de Farmacologia da Dor e Neuromodulação: Investigações Pré-Clínicas, Departamento de Farmacologia, Instituto de Ciências Básicas da Saúde, Universidade Federal do Rio Grande do Sul, 90046-900 Porto Alegre, Brazil.
authors.forename: Iraci L S
authors.initials: IL
authors.lastname: Torres
authors.affiliation: Programa de Pós-Graduação em Ciências Farmacêuticas, Universidade Federal do Rio Grande do Sul, 90610-000 Porto Alegre, Brazil.
authors.forename: Stela Maris Kuze
authors.initials: SM
authors.lastname: Rates