Relaxant effects of petasins in isolated guinea pig trachea and their structure-activity relationships

In the present study, we attempted to compare four petasins, isolated from Petasites formosanus Kitamura, and to look for structure-activity relations hips, which may be helpful for synthesizing more active compounds for the t reatment of asthma. Four petasins, including petasin, isopetasin, S-petasin and S-isopetasin, concentration-dependently relaxed histamine (10 muM)-, c arbachol (0.2 muM)-, KCI (30 mM)-, and leukotriene D-4 (10 nM)-induced prec ontractions of isolated guinea pig tracheais. The IC50 Values strongly show ed that the relaxant effects of the sulfur-containing petasins, S-petasin a nd S-isopetasin, were more potent than those of non-sulfur-containing petas ins, petasin and isopetasin. S-Isopetasin, with IC50 Values around 10 muM, selectively relaxed carbachol- and KCI-induced precontractions, and had alm ost no effects (IC(50)s > 300 muM) on histamine- and leukotriene D-4-induce d precontractions. However, 5-petasin, with IC50 values about 6 -9 muM, non -selectively relaxed the precontractions induced by all these contractile a gents. The influence of isomerization of either petasin to isopetasin or S- petasin to S-isopetasin on the relaxant effects is not clear.