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Relaxant effect of Ent‑7α‑hydroxytrachyloban‑18-oic acid, a trachylobane diterpene from Xylopia langsdorfiana A. St-Hil. & Tul., on tracheal smooth muscle

Ent-7α-hydroxytrachyloban-18-oic acid, a trachylobane diterpene from Xylopia langsdorfiana, has previously been shown to relax the guinea-pig trachea in a concentration-dependent manner. In this study we aimed to elucidate the mechanisms underlying this action and so contribute to the discovery of n...

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Detalles Bibliográficos
Autores principales: Martins, Italo R. R., dos Santos, Rosimeire F., Correia, Ana C. de C., de Oliveira, Gislaine A., Macêdo, Cibério L., Monteiro, Fabio de S., dos Santos, Paula F., Cavalcante, Fabiana de A., Tavares, Josean F., da Silva, Bagnólia A.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Japan Society of Smooth Muscle Research 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5137274/
https://www.ncbi.nlm.nih.gov/pubmed/23832615
http://dx.doi.org/10.1540/jsmr.49.15
Descripción
Sumario:Ent-7α-hydroxytrachyloban-18-oic acid, a trachylobane diterpene from Xylopia langsdorfiana, has previously been shown to relax the guinea-pig trachea in a concentration-dependent manner. In this study we aimed to elucidate the mechanisms underlying this action and so contribute to the discovery of natural products with therapeutic potential. A possible interaction between diterpene and the Ca(2+)-calmodulin complex was eliminated as chlorpromazine (10(-6) M), a calmodulin inhibitor, did not significantly alter the diterpene-induced relaxation (pD(2) = 4.38 ± 0.07 and 4.25 ± 0.07; mean ± S.E.M., n=5). Trachylobane-318 showed a higher relaxant potency when the trachea was contracted by 18 mM KCl than it did with 60 mM KCl (pD(2) = 4.90 ± 0.25 and 3.88 ± 0.01, n=5), suggesting the possible activation of K(+) channels. This was confirmed, as in the presence of 10 mM TEA(+) (a non-selective K(+) channel blocker), diterpene relaxation potency was significantly reduced (pD(2) = 4.38 ± 0.07 to 4.01 ± 0.06, n=5). Furthermore, K(+) channel subtypes K(ATP), K(V), SK(Ca) and BK(Ca) seem to be modulated positively by trachylobane-318 (pD(2) = 3.91 ± 0.003, 4.00 ± 0.06, 3.45 ± 0.14 and 3.80 ± 0.05, n=5) but not the K(ir) subtype channel (pD(2) = 4.15 ± 0.10, n=5). Cyclic nucleotides were not involved as the relaxation due to aminophylline (pD(2) = 4.27 ± 0.09, n=5) was not altered in the presence of 3 × 10(-5) M trachylobane-318 (pD(2) = 4.46 ± 0.08, n=5). Thus, at a functional level, trachylobane-318 seems to relax the guinea-pig trachea by positive modulation of K(+) channels, particularly the K(ATP), K(V), SK(Ca) and BK(Ca) subtypes.