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Abstract Title:

Bronchodilatory effects of S-isopetasin, an antimuscarinic sesquiterpene of Petasites formosanus, on obstructive airway hyperresponsiveness.

Abstract Source:

Neoplasma. 2006;53(5):402-9. PMID: 18348887

Abstract Author(s):

Ling-Hung Lin, Tzu-Jung Huang, Sheng-Hao Wang, Yun-Lian Lin, Sheng-Nan Wu, Wun-Chang Ko

Abstract:

In the presence of neostigmine (0.1 microM), S-isopetasin competitively antagonized cumulative acetylcholine-induced contractions in guinea pig trachealis, because the slope [1.18+/-0.15 (n=6)] of Schild's plot did not significantly differ from unity. The pA2 value of S-isopetasin was calculated to be 4.62+/-0.05 (n=18). The receptor binding assay for muscarinic receptors of cultured human tracheal smooth muscle cells (HTSMCs) was performed using [3H]-N-methylscopolamine ([3H]-NMS). Saturation binding assays were carried out with [3H]-NMS in the presence (non-specific binding) and absence (total binding) of atropine (1 microM). Analysis of the Scatchard plot (y=0.247-1.306x, r2=0.95) revealed that the muscarinic receptor binding sites in cultured HTSMCs constituted a single population (n(H)=1.00). The equilibrium dissociation constant (Kd) and the maximal receptor density (B(max)) for [3H]-NMS binding were 766 pM and 0.189 pmol/mg of protein, respectively. The -logIC50 values of S-isopetasin, methoctramine, and 1,1-Dimethyl-4-diphenylacetoxypiperidinium iodide (4-DAMP) for displacing 0.4 nM [3H]-NMS-specific binding were 5.05, 6.25, and 8.56, respectively, which suggests that [3H]-NMS binding is predominantly on muscarinic M3 receptors of cultured HTSMCs. The inhibitory effects of S-isopetasin on enhanced pause (P(enh)) value were similar to that of ipratropium bromide, a reference drug. The duration of action of S-isopetasin (20 microM), also similar to that of ipratropium bromide (20 microM), was 3 h. In contrast to ipratropium bromide, which non-selectively acts on muscarinic receptors, S-isopetasin preferentially acts on muscarinic M3 receptors. In conclusion, S-isopetasin may be beneficial as a bronchodilator in the treatment of chronic obstructive pulmonary disease and asthma exacerbations.

Study Type : In Vitro Study

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