Abstract
The effect of osthole, isolated from Angelica pubescens, on the contraction of guinea-pig trachea was studied. Osthole (25–100 μmol/l), theophylline (10–1000 μmol/l) and higher concentrations of nifedipine (0.1–100 μmol/l) suppressed the contraction response curves of tracheal smooth muscle caused by carbachol, prostaglandin F2α (PGF2α), U46619 (thromboxane A2 analogue) and leukotriene C4 (LTC4) in a concentration-dependent manner. The contraction caused by high K+ (120 mmol/1) and cumulative concentrations of CaCl2 (0.03–3 mmol/1) was also inhibited concentration-dependently by osthole (25–100 μmol/l), theophyl line(10–1000 μmol/l) and lower concentrations of nifedipine (0.01–0.1 μmol/l). The relaxant actions of osthole were not affected by propranolol (1 μmol/l), glibenclamide (10 μmol/l) or removal of tracheal epithelium. Osthole (100 μmol/l) was still effective in causing tracheal relaxation in the presence of nifedipine (1 μmol/l). In Ca2+-free- and EGTA (0.2 mmol/1)-containing medium, the relaxing effect of osthole was more potent than in normal Krebs solution. Osthole (25 and 50 μmol/l) caused 2.9 and 6.5, or 3.0 and 5.6 fold, respectively, increase in potency of forskolin or sodium nitroprusside in causing tracheal relaxation but did not affect that by cromakalim. Osthole (50 μmol/l) enhanced the increase in tissue cAMP and cGMP levels induced by forskolin and sodium nitroprusside, respectively, and in higher concentrations (100 and 250 μmol/l), itself increased markedly tissue cAMP and cGMP contents. Osthole (10–250 mol/l) inhibited the activity of cAMP and cGMP phosphodiesterases in a concentration-dependent manner. It is concluded that osthole exerts a nonspecific relaxant effect on the trachealis by inhibiting the cAMP and cGMP phosphodiesterases.
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Correspondence to: C. M. Teng at the above address
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Teng, CM., Lin, CH., Ko, FN. et al. The relaxant action of osthole isolated from Angelica pubescens in guinea-pig trachea. Naunyn-Schmiedeberg's Arch Pharmacol 349, 202–208 (1994). https://doi.org/10.1007/BF00169838
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DOI: https://doi.org/10.1007/BF00169838