Relaxant effects of forskolin on guinea pig tracheal smooth muscle

We investigated the relaxant effects of forskolin, a diterpene derivative isolated from the roots of Coleus forskohlii, on guinea pig airway smooth muscle by measuring the isometric tension of tracheal smooth muscle in vitro and transcutaneous Po2 during the histamine inhalation test (HIT) in vivo. Forskolin (10(-9)-10(-5) M) caused dose-dependent relaxant effects on resting tone and on leukotriene C4 (10(-7) M)-, leukotriene D4 (10(-7) M)-, and carbachol (3 X 10(-6) M)-induced contraction of tracheal smooth muscle. Moreover, with propranolol pretreatment the relaxant effect of forskolin on tracheal smooth muscle did not change, whereas with the same pretreatment the relaxant effect of isoproterenol diminished. Forskolin (10(-8)-10(-6) M) raised tissue cyclic AMP levels dose-dependently in tracheal smooth muscle (6.7-359.9 pmol/mg protein). Forskolin (1 mg/kg) administered subcutaneously raised the respiratory threshold of (RT-histamine in the HIT. The determination of the RT-histamine by measuring tcPo2 was possible without anesthesia. These results suggest that forskolin relaxes airway smooth muscle in guinea pigs in vitro and in vivo by raising tissue cyclic AMP levels and that its actions are independent of beta-adrenoceptors.