Effect of Kil769, a novel K(+)-channel opener, on sensitivity to Ca2+ of contractile elements and inositol phosphate formation in porcine coronary artery

J Pharm Pharmacol. 1995 Feb;47(2):148-51. doi: 10.1111/j.2042-7158.1995.tb05768.x.

Abstract

To determine whether Kil769, a novel K(+)-channel opener, acts intracellularly in vasorelaxation, we compared the effects of Kil769 on force of contraction, intracellular Ca2+ concentration ([Ca2+]i) and inositol phosphate (IP1) formation with those of Ca(2+)-channel blockers in isolated porcine coronary artery. Kil769 (10 microM) and verapamil (1 microM), which produced submaximal relaxation, reduced the increase in [Ca2+]i and force of contraction induced by 25 mM KCl. Verapamil reduced [Ca2+]i and the force of contraction to a similar extent but Kil769 reduced force of contraction more strongly than it did [Ca2+]i. Kil769 also inhibited U46619 (9,11-dideoxy-9 alpha,11 alpha-methano-epoxy-PGF2 alpha)-induced IP1 formation and glibenclamide blocked its inhibitory effect. These results suggest that the opening of K+ channels induced by Kil769 reduces the Ca2+ sensitivity of contractile elements and inositol phospholipid hydrolysis which is related to the Ca2+ release from intracellular storage.

Publication types

  • Comparative Study

MeSH terms

  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
  • Animals
  • Calcium / metabolism*
  • Calcium Channel Blockers / pharmacology
  • Coronary Vessels / drug effects
  • Coronary Vessels / metabolism
  • Dose-Response Relationship, Drug
  • Fura-2 / chemistry
  • Glyburide / pharmacology
  • Hydrolysis
  • In Vitro Techniques
  • Inositol Phosphates / biosynthesis*
  • Muscle Contraction / drug effects
  • Muscle Relaxation / drug effects
  • Muscle, Smooth, Vascular / drug effects*
  • Potassium Channels / drug effects*
  • Prostaglandin Endoperoxides, Synthetic / pharmacology
  • Pyridines / pharmacology*
  • Swine
  • Thromboxane A2 / analogs & derivatives
  • Thromboxane A2 / pharmacology
  • Vasoconstrictor Agents / pharmacology
  • Vasodilator Agents / pharmacology*
  • Verapamil / pharmacology

Substances

  • Calcium Channel Blockers
  • Inositol Phosphates
  • Potassium Channels
  • Prostaglandin Endoperoxides, Synthetic
  • Pyridines
  • Vasoconstrictor Agents
  • Vasodilator Agents
  • Ki 1769
  • Thromboxane A2
  • 15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
  • Verapamil
  • Glyburide
  • Calcium
  • Fura-2