THE RELAXANT ACTION OF OSTHOLE ISOLATED FROM ANGELICA-PUBESCENS IN GUINEA-PIG TRACHEA

The effect of osthole, isolated from Angelica pubescens, on the contraction of guinea-pig trachea was studied. Osthole (25 - 100 mu mol/l), theophylline (10 - 1000 mu mol/l) and higher concentrations of nifedipine (0.1 - 100 mu mol/l) suppressed the contraction response curves of tracheal smooth muscle caused by carbachol, prostaglandin F-2 alpha (PGF(2 alpha)), U46619 (thromboxane A(2) analogue) and leukotriene C-4 (LTC(4)) in a concentration-dependent manner. The contraction caused by high K+ (120 mmol/l) and cumulative concentrations of CaCl2 (0.03 - 3 mmol/l) was also inhibited concentration-dependently by osthole (25 - 100 mu mol/l), theophylline (10 - 1000 mu mol/l) and lower concentrations of nifedipine (0.01 - 0.1 mu mol/l). The relaxant actions of osthole were not affected by propranolol (1 mu mol/l), glibenclamide (10 mu mol/l) or removal of tracheal epithelium. Osthole (100 mu mol/l) was still effective in causing tracheal relaxation in the presence of nifedipine (1 mu mol/l). In Ca2+-free- and EGTA (0.2 mmol/l)-containing medium, the relaxing effect of osthole was more potent than in normal Krebs solution. Osthole (25 and 50 mu mol/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 mu mol/l) enhanced the increase in tissue cAMP and cGMP levels induced by forskolin and sodium nitroprusside, respectively, and in higher concentrations (100 and 250 mu mol/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.