title: Relaxant effect of Ent-7α-hydroxytrachyloban-18-oic acid, a trachylobane diterpene from Xylopia langsdorfiana A. St-Hil. & Tul., on tracheal smooth muscle.
abstract: 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 (pD2 = 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 (pD2 = 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 (pD2 = 4.38 ± 0.07 to 4.01 ± 0.06, n=5). Furthermore, K(+) channel subtypes KATP, KV, SKCa and BKCa seem to be modulated positively by trachylobane-318 (pD2 = 3.91 ± 0.003, 4.00 ± 0.06, 3.45 ± 0.14 and 3.80 ± 0.05, n=5) but not the Kir subtype channel (pD2 = 4.15 ± 0.10, n=5). Cyclic nucleotides were not involved as the relaxation due to aminophylline (pD2 = 4.27 ± 0.09, n=5) was not altered in the presence of 3 × 10(-5) M trachylobane-318 (pD2 = 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 KATP, KV, SKCa and BKCa subtypes.
authors.affiliation: Centro de Ciências da Saúde, Universidade Federal da Paraíba (UFPB), João Pessoa, Paraíba, Brazil.
authors.forename: Italo R R
authors.initials: IR
authors.lastname: Martins
authors.forename: Rosimeire F
authors.initials: RF
authors.lastname: Dos Santos
authors.forename: Ana C
authors.initials: AC
authors.lastname: de C Correia
authors.forename: Gislaine A
authors.initials: GA
authors.lastname: de Oliveira
authors.forename: Cibério L
authors.initials: CL
authors.lastname: Macêdo
authors.forename: Fabio
authors.initials: F
authors.lastname: de S Monteiro
authors.forename: Paula F
authors.initials: PF
authors.lastname: Dos Santos
authors.forename: Fabiana
authors.initials: F
authors.lastname: de A Cavalcante
authors.forename: Josean F
authors.initials: JF
authors.lastname: Tavares
authors.forename: Bagnólia A
authors.initials: BA
authors.lastname: da Silva
mesh_terms: D000818:Animals; D004224:Diterpenes / Q000302:isolation & purification / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects*; D009130:Muscle, Smooth / Q000187:drug effects*; D015221:Potassium Channels / Q000145:classification / Q000378:metabolism; D014132:Trachea / Q000187:drug effects*; D054336:Xylopia / Q000737:chemistry*
chemical_list: D004224:Diterpenes; D015221:Potassium Channels; C572781:ent-7alpha-hydroxytrachyloban-18-oic acid