Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/39935
Title: 7-Epiclusianone, a tetraprenylated benzophenone, relaxes airway smooth muscle through activation of the nitric oxide-cGMP pathway
Authors: Coelho, Luciana Pontes
Serra, Magda Fráguas
Pires, Ana Lúcia de Aguiar
Cordeiro, Renato Sérgio Balão
Silva, Patrícia Machado Rodrigues e
Santos, Marcelo Henrique dos
Martins, Marco Aurélio
Affilliation: Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil.
Universidade Federal de Alfenas. Departamento de Farmácia. Laboratório de Fitoquímica e Medicamentos e Química. Alfenas, MG, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Inflamação. Rio de Janeiro, RJ, Brasil.
Abstract: This study was undertaken to investigate the putative mechanism(s) underlying the antispasmodic effect of 7-epiclusianone, a naturally occurring compound isolated from the plant Garcinia brasiliensis. Guinea pig tracheal rings were mounted in tissue baths filled with Krebs' solution, and the contractile response to distinct stimuli was measured in the presence or absence of 7-epiclusianone. We also tested the effect of 7-epiclusianone on methacholine-evoked airways obstruction in BALB/c mice using barometric plethysmography. 7-Epiclusianone (10 microM) inhibited epithelium-intact tracheal ring contraction induced by allergen, histamine, 5-hydroxytryptamine, or carbachol challenge. The relaxation effect was abrogated by epithelium removal, the presence of nitric-oxide synthase inhibitor N(omega)-nitro-L-arginine methyl ester (L-NAME) (100 microM), or soluble guanylate cyclase inhibitor 1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) (10 microM). 7-Epiclusianone (1-100 microM) induced a dose-dependent increase in the intracellular cGMP levels of cultured tracheal rings. The relaxation effect of 7-epiclusianone was also inhibited by K(+) channel blockers tetraethylammonium (10 microM), glibenclamide (1 microM), or apamin (1 microM), but not by 9-(tetrahydro-2'-furyl)adenine (SQ22,536) (100 microM), an adenylate cyclase inhibitor. In epithelium-intact tracheal rings, 7-epiclusianone also inhibited Ca(2+)-induced contractions in K(+) (60 mM)-depolarized preparations, but it seemed ineffective in assays in which epithelium-denuded tracheal ring preparations were used. Oral administration of 7-epiclusinone (25-100 mg/kg) dose-dependently inhibited airway obstruction triggered by aerosolized methacholine (6-25 mg/ml), in a mechanism sensitive to L-NAME (20 mg/kg). In conclusion, the relaxation effect of 7-epiclusinone seems to be mediated by epithelium-, nitric oxide-, and cGMP-dependent mechanisms. Furthermore, oral administration of 7-epiclusianone reduces episodes of bronchial obstruction, warranting further research on this compound regarding a putative application in asthma therapy.
Keywords: 7-Epiclusianone
Tetraprenylated Benzophenone
Nitric Oxide-cGMP
Músculo liso das vias aéreas
keywords: 7-Epiclusianona
Benzofenona tetraprenilada
Airway Smooth Muscle
Óxido nítrico-cGMP
Issue Date: 2008
Publisher: American Society for Pharmacology and Experimental Therapeutics
Citation: COELHO, Luciana Pontes et al. 7-Epiclusianone, a Tetraprenylated Benzophenone, Relaxes Airway Smooth Muscle through Activation of the Nitric Oxide-cGMP Pathway. Journal of Pharmacology and Experimental Therapeutics, v. 327, n. 1, p. 206-214, 2008.
DOI: 10.1124/jpet.108.138032
ISSN: 0022-3565
Copyright: restricted access
Appears in Collections:IOC - Artigos de Periódicos

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