Involvement of K(+) channels in the relaxant effects of YC-1 in vascular smooth muscle

Eur J Pharmacol. 1999 Oct 1;382(1):11-8. doi: 10.1016/s0014-2999(99)00574-9.

Abstract

This study addresses the question whether K(+) channels are involved in the vasorelaxant effects of 3-(5'-hydroxymethyl-2'-furyl)-1-benzyl-indazole (YC-1 ). In rat aorta, guinea pig aorta, and guinea pig a. carotis, YC-1 inhibited contractions induced by phenylephrine (3 microM) more potently than those induced by K(+)(48 mM). In rat aorta, tetraethylammonium (10 mM), charybdotoxin (0.2 microM), and iberiotoxin (0.1 microM), but not glibenclamide (10 microM), attenuated the relaxant effects of YC-1. In guinea pig a. carotis, YC-1 (30 microM) induced a hyperpolarisation which was antagonised by 1H-[1,2,4]oxadiazolo[4, 3-a]quinoxalin-1-one (ODQ; 50 microM). In rat aorta, YC-1 (30 microM) increased the rate constant of 86Rb-efflux. The effect of YC-1 was potentiated by zaprinast (10 microM), but inhibited by ODQ (50 microM) or charybdotoxin (0.2 microM). In smooth muscle cells from rat aorta, YC-1 (10 microM) increased BK(Ca) channel activity. It is suggested that YC-1-induced vasorelaxation is partially mediated by the activation of K(+) channels.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Aorta, Thoracic / drug effects
  • Carotid Arteries / drug effects
  • Dose-Response Relationship, Drug
  • Drug Interactions
  • Female
  • Guinea Pigs
  • In Vitro Techniques
  • Indazoles / pharmacology*
  • Male
  • Membrane Potentials / drug effects
  • Muscle Relaxation / drug effects
  • Muscle, Smooth, Vascular / drug effects*
  • Muscle, Smooth, Vascular / physiology
  • Phenylephrine / pharmacology
  • Potassium / physiology*
  • Potassium Channels / physiology*
  • Rats
  • Rats, Sprague-Dawley
  • Time Factors
  • Vasodilation / drug effects*

Substances

  • Indazoles
  • Potassium Channels
  • 3-(5'-hydroxymethyl-2'-furyl)-1-benzylindazole
  • Phenylephrine
  • Potassium