The pharmacological activity of atherosperminine, isolated from Fissistigma glaucescens, was determined in isolated guinea-pig trachealis. Atherosperminine (25-100 μM) and theophylline (10-1000 μM) both inhibited the contractile response caused by carbachol, prostaglandin F2α (PGF2α), U46619 (thromboxane A2 analogue), leukotriene C4 (LTC4) and Ca2+ (in the presence of 120 mM KCl) in a concentration-dependent manner. The inhibition was characterized by a rightwards shift of the concentration-response curves with supression of the maximal contraction. Propranolol (1 μM), glibenclamide (10 μM) and removal of tracheal epithelium did not modify the relaxant action of atherosperminine. Atrosperminine (25 and 50 μM) caused a 2.4- and 5.0-fold, respectively, potentiation of the action of forskolin to cause trachel relaxation but did not potentiate the action of sodium nitroprusside or cromakalim. Atherosperminine (50 μM) potentiated the action of forskolin to increase tissue cAMP content and, in higher concentrations (100 and 250 μM), itself increased tissue cAMP but not cGMP content. Astherosperminine markedly inhibited cAMP phosphodieterase but not cGMP phosphodieterase in homogenates of guinea-pig trachealis. It is concluded that atherosperminine exerts a non-specific relexant effect on the trachealis. Its major mechanism of action appears to be inhibition of cAMP phosphodiesterase, perhaps with a minor effect of cAMP phosphodiesterase at higher concentrations.
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