This study was undertaken to assess the effects of eugenol (EUG) on tracheal muscle (TM) and the putative mechanisms underlying these effects. Cumulatively increasing concentrations (1-1000 μm) of EUG did not affect the resting tonus of TM. However, EUG (1-2000 μm) reduced the contractions induced by electrical field stimulation (IC(50) = 842.3 ± 52.7 μm), an effect that was unaltered by either 10 μm montelukast (IC(50) = 816.1 ± 70.1 μm) or 2 μm indomethacin (IC(50) = 693.1 ± 170.8 μm). EUG also completely relaxed the sustained contractile responses to 80 mM K(+) (IC(50) = 597.3 ± 60.6 μm) and 1 μm carbamoylcholine (IC(50) = 571.3 ± 148.8 μm), an effect that was unaltered by indomethacin (2 μm). Under Ca(2+) -free conditions, EUG reduced the ACh-induced contractions (IC(50) = 703.4 ± 256.1 μm), the CaCl₂ -induced contractions in preparations pretreated with 60 μm ACh in the presence of nifedipine, and the Ba(2+) -induced contractions in preparations depolarized with K(+) . In tracheal preparations maintained in Ca(2+) -containing solution, EUG (300-2000 μm) relaxed the contractile response to phorbol dibutyrate (1 μm), an activator of protein kinase C. It is concluded that in TM, EUG induces a myogenic antispasmodic effect (not modulated by arachidonic acid derivatives) either through various mechanisms almost with the same pharmacological potency or via an action on a step common to all of them. These mechanisms seem to include blockade of voltage- and receptor-operated Ca(2+) channels, IP₃ -induced Ca(2+) release from sarcoplasmic reticulum and reduction of the sensitivity of contractile proteins to Ca(2+) .
2010 The Authors Fundamental and Clinical Pharmacology. 2010 Société Française de Pharmacologie et de Thérapeutique.