Antispasmodic effects of eugenol on rat airway smooth muscle

作者:Lima Felipe Crescencio; Peixoto Neves Dieniffer; Moreira Gomes Maria Diana; Coelho de Souza Andrelina Noronha; Lima Crystianne Calado; Zin Walter Araujo; Caldas Magalhaes Pedro Jorge; Saad Lahlou; Leal Cardoso Jose Henrique*
来源:Fundamental & Clinical Pharmacology, 2011, 25(6): 690-699.
DOI:10.1111/j.1472-8206.2010.00892.x

摘要

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 mu M) of EUG did not affect the resting tonus of TM. However, EUG (1-2000 mu M) reduced the contractions induced by electrical field stimulation (IC50 = 842.3 +/- 52.7 mu M), an effect that was unaltered by either 10 mu M montelukast (IC50 = 816.1 +/- 70.1 mu M) or 2 mu M indomethacin (IC50 = 693.1 +/- 170.8 mu M). EUG also completely relaxed the sustained contractile responses to 80 mM K+ (IC50 = 597.3 +/- 60.6 mu M) and 1 mu M carbamoylcholine (IC50 = 571.3 +/- 148.8 mu M), an effect that was unaltered by indomethacin (2 mu M). Under Ca2+-free conditions, EUG reduced the ACh-induced contractions (IC50 = 703.4 +/- 256.1 mu M), the CaCl2-induced contractions in preparations pretreated with 60 mu M ACh in the presence of nifedipine, and the Ba2+-induced contractions in preparations depolarized with K+. In tracheal preparations maintained in Ca2+-containing solution, EUG (300-2000 mu M) relaxed the contractile response to phorbol dibutyrate (1 mu M), 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 Ca2+ channels, IP3-induced Ca2+ release from sarcoplasmic reticulum and reduction of the sensitivity of contractile proteins to Ca2+.

  • 出版日期2011-12