Participação dos canais de potássio no efeito relaxante do ácido ent-7a-hidroxitraquiloban-18-oico em traqueia isolada de cobaia / Participation of potassium channels in the ent-7a-hidroxitrachyloban-18-oic acid relaxation effect on guinea pig trachea

AUTOR(ES)
FONTE

IBICT - Instituto Brasileiro de Informação em Ciência e Tecnologia

DATA DE PUBLICAÇÃO

17/02/2012

RESUMO

From Xylopia langsdorfiana A. St-Hil. &Tul. stem bark was isolated the diterpene of trachylobane class, ent-7α-hydroxytrachyloban-18-oic acid (trachylobane-318) that in previous studies showed to be able to relax guinea-pig trachea pre-contracted by carbachol (CCh). Thus, we aimed to investigate the action mechanism underlying in this trachylobane-318 relaxant activity. Trachea rings were suspended in organ baths, containing Krebs solution, at 37 C and aired with carbogenic mixture. Isometric contractions were registered using a digital acquisition system. In order to evaluate a direct effect of the diterpene in Ca2+-calmodulin complex was used chlorpromazine (CPZ) (10-6 M), a calmodulin inhibitor, and we observed that trachylobane-318 relaxation effect (pD2 = 4.38 0.07, n = 5) was not significantly altered in presence of this inhibitor (pD2 = 4.25 0.07, n = 5). Then, was performed a protocol using different potassium (K+) extracellular concentrations which indicated that trachylobane-318 would be acting as a possible potassium channels activator since its relaxation was more potent when guinea-pig trachea was pre-contracted by KCl 18 mM (pD2 = 4.90 0.25, n = 5) than by KCl 60 mM (pD2 = 3.88 0.01, n = 5). To confirm the potassium channels participation was used a non-selective potassium channels blocker, tetraethylammonium (TEA+) 10 mM, that was pre-incubated before CCh addition, that resulted in an attenuation of diterpene relaxation (pD2 = 4.01 0.06, n = 5). To determinate which potassium channels subtypes would be involved in the trachylobane-318 action, the diterpene relaxation curve was assessed in the presence of several potassium channels selective blockers. The fact of the trachylobane-318 relaxation curve was shifted to the right in a significant manner in the presence of 4-AP, a selective blocker of voltage activated K+ channels (Kv) (pD2 = 4.00 0.06, n = 5); glibenclamide, a selective blocker of ATP-sensitive K+ channel (KATP) (pD2 = 3.91 0.003, n = 5); apamin, a selective blocker of small conductance calcium-activated K+ channels (SKCa) (3.45 0.14, n = 5) and big conductance calcium-activated K+ channels (BKCa) (3,80 0,05, n = 5) is suggestive that the diterpene is modulating positively these channels to exert its relaxant effect. On the other hand, the inwardly rectifying K+ channels (Kir) was discarded since the relaxation curve was not altered (pD2 = 4.15 0.10, n = 5) in the presence of BaCl2, selective blocker of these channels. Cyclic nucleotides participation was discarded since the relaxation curve obtained with aminophylline on guinea-pig contracted by CCh (pD2 = 4.27 0.09, n = 5), a phosphodiesterases (PDEs) non-selective inhibitor, was not altered in trachylobane-318 presence (pD2 = 4.46 0.08, n = 5). Thus, trachylobane-318 relaxant effect seems to involve the positive modulation of potassium channels subtypes Kv, KATP, SKCa and BKCa on guinea pig trachea.

ASSUNTO(S)

annonaceae xylopia langsdorfiana traquilobano diterpeno canais de potássio músculo liso das vias aéreas farmacologia airway smooth muscle potassium channels diterpene trachylobane xylopia langsdorfiana annonaceae

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