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 relationships, which may be helpful for synthesizing more active compounds for the treatment of asthma. Four petasins, including petasin, isopetasin, S-petasin and S-isopetasin, concentration-dependently relaxed histamine (10 microM)-, carbachol (0.2 microM)-, KCl (30 mM)-, and leukotriene D4 (10 nM)-induced precontractions of isolated guinea pig trachealis. The IC50 values strongly showed that the relaxant effects of the sulfur-containing petasins, S-petasin and S-isopetasin, were more potent than those of non-sulfur-containing petasins, petasin and isopetasin. S-isopetasin, with IC50 values around 10 microM, selectively relaxed carbachol- and KCl-induced precontractions, and had almost no effects (IC50s > 300 microM) on histamine- and leukotriene D4-induced precontractions. However, S-petasin, with IC50 values about 6-9 microM, non-selectively relaxed the precontractions induced by all these contractile agents. The influence of isomerization of either petasin to isopetasin or S-petasin to S-isopetasin on the relaxant effects is not clear.
Ko
W C
WC
Lei
C B
CB
Lin
Y L
YL
Chen
C F
CF
D000818:Animals; D019659:Asteraceae / Q000737:chemistry*; D006168:Guinea Pigs; D066298:In Vitro Techniques; D008297:Male; D009126:Muscle Relaxation / Q000187:drug effects; D012717:Sesquiterpenes / Q000302:isolation & purification* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014132:Trachea / Q000187:drug effects* / Q000502:physiology
D012717:Sesquiterpenes; C418727:petasin; C418728:isopetasin