Effects of esculetin (6,7-dihydroxycoumarin) on guinea-pig tracheal chains in vitro

Esculetin (6,7-dihydroxycoumarin) was tested in isolated guinea-pig tracheal chains from normal and ovalbumin-sensitized animals. The drug showed a concentration-dependent relaxant effect, with an EC50 of 60 microM. Pretreatment with esculetin (30-60 microM) was not able to reduce the contractile response induced by either carbachol (0.1 microM), histamine (10 microM), BaCl2 (10 mM) or K+ (80 mM). Esculetin increased the contraction evoked by PGF2 alpha and by histamine, but reduced A23187-induced contraction. Mepacrine (10 microM), a phospholipase A2 inhibitor, reduced the relaxant effect of the lower esculetin concentrations (3-60 microM). Indomethacin (0.1 microM) increased the relaxation induced by esculetin (3-10 microM). In tracheal chains from ovalbumin-sensitized guinea-pigs, esculetin (60 microM) significantly reduced the duration of the recovery phase after antigen challenge contraction. In conclusion, in our in vitro conditions, this natural coumarin derivative seems to act by interfering with the arachidonic acid cascade.