Mechanisms of relaxant action of S-petasin and S-isopetasin, sesquiterpenes of Petasites formosanus, in isolated guinea pig trachea

We investigated the mechanisms of action of S-petasin and S-isopetasin, fro m Petasites formosanus Kitamura which is used as a folk medicine for treati ng hypertension, tumors, and asthma in Taiwan. The tension changes of trach eal segments were isometrically recorded on a polygraph, S-Petasin and S-is opetasin non-competitively inhibited cumulative histamine; and carbachol-in duced contractions with an exception that S-isopetasin produced a parallel, rightward shift of the concentration-response curve of carbachol in a comp etitive manner. S-Petasin also non-competitively inhibited cumulative Ca2+- induced contractions in depolarized (K+, 60 mM; histamine, 100 muM; or carb achol, 10 muM) guinea-pig tracheas. S-Isopetasin did in depolarized (K+, 60 mM) trachea too. The nifedipine (10 muM)-remaining tension of carbachol (0 .2 muM)-induced precontraction was further relaxed by S-petasin or S-isopet asin, suggesting that no matter whether either blocked VDCCs or not, S-peta sin or S-isopetasin may have other mechanisms of relaxant action. The relax ant effect of S-petasin or S-isopetasin was unaffected by the presence of p ropranolol (1 muM). 2',5'-dideoxyadenosine (10 muM), methylene blue (25 muM ), glibenclamide (10 muM), NW-nitro-L-arginine (20 muM), or alpha -chymotry psin (1 U/ml). However, S-petasin (100-300 muM), but not S-isopetasin, sign ificantly inhibited cAMP-, but not cGMP-dependent PDE activity of the trach ealis. The above results reveal that the mechanisms of relaxant action of S -petasin and S-isopetasin may be primarily due to its non-specific antispas modic and antimuscarinic effects, respectively.