Mechanisms underlying the relaxation induced by isokaempferide from Amburana cearensis in the guinea-pig isolated trachea

Life Sci. 2006 May 30;79(1):98-104. doi: 10.1016/j.lfs.2005.12.024. Epub 2006 Feb 7.

Abstract

The present study examines possible mechanisms by which the flavonoid isokaempferide (IKPF; 5,7,4'-trihydroxy-3-methoxyflavone) from Amburana cearensis, a Brazilian medicinal plant popularly used as bronchodilator, induces relaxation of guinea-pig isolated trachea. In the trachea (with intact epithelium) contracted by carbachol, IKPF (1-1000 microM) caused a graded relaxation, and the epithelium removal increased the sensitivity of the airway smooth muscle to IKPF (EC50, in intact tissue: 77.4 [54.8-109.2] microM; in denuded epithelium: 15.0 [11.3-20.1] microM). The IKPF-induced relaxation was inhibited in 41% by the nitric oxide (NO) synthase inhibitor L-NAME (100 microM); in 31% and 50% by the soluble guanylate cyclase (sGC) inhibitor ODQ (3 and 33 microM); by propranolol (31%) and also by capsaicin (37%). In the trachea pre-contracted by 40 mM KCl the pre-incubation with glibenclamide (33 microM) or iberiotoxin (IbTX, 0.1 microM), selective K(+) channel inhibitors, inhibited the IKPF-induced relaxation by 39% and 38%, respectively. On the other hand, 4-aminopyridine (100 microM), a nonselective K(+) channel antagonist, did not significantly influence the effect of IKPF, while IbTX induced a rightward displacement of the IKPF concentration-response curve. However, in muscle pre-contracted with 120 mM KCl the relaxant effect of IKPF was significantly reduced and not affected by glibenclamide. In conclusion, these results indicate a direct and epithelium-independent relaxant effect of IKPF on smooth muscle fibers. Although this IKPF relaxant action seems to be multi-mediated, it occurs via both Ca(2+) and ATP-sensitive K(+) channels, but some other possible mechanisms unrelated to K(+) channels cannot be excluded.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adrenergic beta-Antagonists / pharmacology
  • Animals
  • Capsaicin / pharmacology
  • Carbachol / pharmacology
  • Coumarins / pharmacology
  • Enzyme Inhibitors / pharmacology
  • Flavonoids / chemistry
  • Flavonoids / pharmacology*
  • Guanylate Cyclase / antagonists & inhibitors
  • Guinea Pigs
  • Histamine / pharmacology
  • In Vitro Techniques
  • Muscarinic Agonists / pharmacology
  • Muscle Relaxation / drug effects
  • Muscle, Smooth / drug effects*
  • NG-Nitroarginine Methyl Ester / antagonists & inhibitors
  • NG-Nitroarginine Methyl Ester / pharmacology
  • Plant Bark / chemistry
  • Plant Extracts / chemistry
  • Plants / chemistry*
  • Potassium Channel Blockers / pharmacology
  • Potassium Chloride / pharmacology
  • Trachea / drug effects*

Substances

  • Adrenergic beta-Antagonists
  • Coumarins
  • Enzyme Inhibitors
  • Flavonoids
  • Muscarinic Agonists
  • Plant Extracts
  • Potassium Channel Blockers
  • isokaempferide
  • Potassium Chloride
  • Histamine
  • Carbachol
  • coumarin
  • Guanylate Cyclase
  • Capsaicin
  • NG-Nitroarginine Methyl Ester