Ent-7 alpha-acetoxytrachyloban-18-oic acid and ent-7 alpha-hydroxytrachyloban-18-oic acid from Xylopia langsdorfiana A. St-Hil. & Tul. modulate K+ and Ca2+ channels to reduce cytosolic calcium concentration on guinea pig ileum

Ent-7 alpha-acetoxytrachyloban-18-oic acid and ent-7 alpha-hydroxytrachyloban-18-oic acid from Xylopia langsdorfiana A. St-Hil. & Tul. modulate K+ and Ca2+ channels to reduce cytosolic calcium concentration on guinea pig ileum

Author Santos, Rosimeire F. Google Scholar
Martins, Italo R. R. Google Scholar
Travassos, Rafael A. Google Scholar
Tavares, Josean F. Google Scholar
Silva, Marcelo S. Google Scholar
Paredes-Gamero, Edgar Julian Autor UNIFESP Google Scholar
Ferreira, Alice Teixeira Autor UNIFESP Google Scholar
Nouailhetas, Viviane Louise Andree Autor UNIFESP Google Scholar
Aboulafia, Jeannine Autor UNIFESP Google Scholar
Rigoni, Vera Lucia Silva Autor UNIFESP Google Scholar
Silva, Bagnolia A. da Google Scholar
Institution Univ Fed Paraiba
Univ Fed Piaui
Universidade Federal de São Paulo (UNIFESP)
Abstract In this study we investigated the mechanism underlying the spasmolytic action of ent-7 alpha-acetoxytrachyloban- 18-oic acid (trachylobane-360) and ent-7 alpha-hydroxytrachyloban-18-oic acid (trachylobane-318), diterpenes obtained from Xylopia langsdorfiana, on guinea pig ileum. Both compounds inhibited histamine-induced cumulative contractions (slope=3.5 +/- 0.9 and 4.4 +/- 0.7) that suggests a noncompetitive antagonism to histaminergic receptors. CaCl2-induced contractions were nonparallelly and concentration-dependently reduced by both diterpenes, indicating blockade of calcium influx through voltage-dependent calcium channels (Ca-v). the Ca-v participation was confirmed since both trachylobanes equipotently relaxed ileum pre-contracted with S-(-)-Bay K8644 (EC50=3.5 +/- 0.7x10-(5) and 1.1 +/- 0.2x10-(5) M) and KCl (EC50=5.5 +/- 0.3x10-(5) and 1.4 +/- 0.2x10-(5) M). K+ channels participation was confirmed since diterpene-induced relaxation curves were significantly shifted to right in the presence of 5 mM tetraethylammonium (TEA(+)) (EC50=0.5 +/- 0.04x10-(4) and 2.0 +/- 0.5x10-(5) M). ATP-sensitive K+ channel (K-ATP), voltage activated K+ channels (K-V), small conductance calcium-activated K+ channels (SKCa) or big conductance calciuma-ctivated K+ channels (BKCa) did not seem to participate of trachylobane-360 spasmolytic action. However trachylobane-318 modulated positively K-ATP, K-V and SKCa (EC50=1.1 +/- 0.3x10-(5), 0.7 +/- 0.2x10-(5) and 0.7 +/- 0.2x10-(5) M), but not BKCa. A fluorescence analysis technique confirmed the decrease of cytosolic calcium concentration ([Ca2+](c)) induced by both trachylobanes in ileal myocytes. in conclusion, trachylobane-360 and trachylobane-318 induced spasmolytic activity by K+ channel positive modulation and Ca2+ channel blockade, which results in [Ca2+](c) reduction at cellular level leading to smooth muscle relaxation. (C) 2011 Published by Elsevier B. V.
Keywords Intestinal smooth muscle
Spasmolytic activity
Diterpene
Xylopia langsdorfiana
Ionic channels
Calcium
Language English
Sponsor Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)
Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)
FAPESQ-PB
Date 2012-03-05
Published in European Journal of Pharmacology. Amsterdam: Elsevier B.V., v. 678, n. 1-3, p. 39-47, 2012.
ISSN 0014-2999 (Sherpa/Romeo, impact factor)
Publisher Elsevier B.V.
Extent 39-47
Origin http://dx.doi.org/10.1016/j.ejphar.2011.12.028
Access rights Open access Open Access
Type Article
Web of Science ID WOS:000300731400006
URI http://repositorio.unifesp.br/handle/11600/34703

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