L-type Ca2+ channels activation and contraction elicited by myricetin on vascular smooth muscles

Naunyn Schmiedebergs Arch Pharmacol. 2003 Dec;368(6):470-8. doi: 10.1007/s00210-003-0836-y. Epub 2003 Nov 15.

Abstract

The effects of myricetin (3,3',4',5,5',7-hesahydroxyflavone), a natural flavonoid found in edible plants, were studied on vascular smooth muscle L-type Ca(2+) channels by comparing its mechanical, radioligand binding, and electrophysiological properties to those of the Ca(2+) channel agonist (S)-(-)-Bay K 8644. In rat aorta rings, both myricetin and (S)-(-)-Bay K 8644 induced contractile responses, which were dependent upon prior exposure to K(+). At 15 mM K(+) (K15) the pEC(50) values for myricetin and (S)-(-)-Bay K 8644 were 4.43+/-0.03 and 7.92+/-0.13, respectively. Furthermore, the maximum tension response to myricetin was not significantly different from that elicited by either (S)-(-)-Bay K 8644 or K60. The Ca(2+) channel blockers nifedipine, verapamil and diltiazem antagonised and fully reverted myricetin-, (S)-(-)-Bay K 8644- as well as K60-induced contractions. Both myricetin and (S)-(-)-Bay K 8644 potentiated rat aorta ring responses to K(+), shifting the K(+) concentration-response curve to the left. (S)-(-)-Bay K 8644, but not myricetin, inhibited in a concentration-dependent manner (+)-[(3)H]PN200-110 binding in porcine aortic membranes. Electrophysiological recordings from single rat tail artery myocytes, under amphotericin B-perforated as well as conventional methods, showed that both myricetin and (S)-(-)-Bay K 8644 increased L-type Ba(2+) current (I(Ba(L))) and shifted the maximum of the current-voltage relationship by 10 mV in the hyperpolarising direction, without, however, modifying the threshold potential. Furthermore, (S)-(-)-Bay K 8644 accelerated both activation and inactivation kinetics of I(Ba(L)) while myricetin slowed down the activation kinetics. Finally, both (S)-(-)-Bay K 8644 and myricetin slowed down deactivation kinetics of I(Ba(L)). These results suggest that myricetin induces vasoconstriction by activating L-type Ca(2+) channel with similar efficacy but a site of action different to that of (S)-(-)-Bay K 8644.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / antagonists & inhibitors
  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / pharmacology
  • Animals
  • Aorta / drug effects
  • Aorta / metabolism
  • Arteries
  • Calcium Channel Agonists / pharmacology
  • Calcium Channel Blockers / pharmacology
  • Calcium Channels, L-Type / drug effects*
  • Calcium Channels, L-Type / physiology
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Electrophysiology
  • Flavonoids / antagonists & inhibitors
  • Flavonoids / pharmacology*
  • In Vitro Techniques
  • Male
  • Muscle Contraction / drug effects
  • Muscle Contraction / physiology
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / physiology
  • Myocytes, Smooth Muscle / drug effects
  • Myocytes, Smooth Muscle / physiology
  • Patch-Clamp Techniques
  • Potassium / pharmacology
  • Radioligand Assay
  • Rats
  • Rats, Wistar
  • Swine
  • Tail

Substances

  • Calcium Channel Agonists
  • Calcium Channel Blockers
  • Calcium Channels, L-Type
  • Flavonoids
  • 3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester
  • myricetin
  • Potassium