Platelet-activating factor activates cardiac GK via arachidonic acid metabolites

FEBS Lett. 1991 Sep 9;289(2):239-43. doi: 10.1016/0014-5793(91)81079-n.


Platelet-activating factor (PAF), added to the bathing solution, stimulated the cardiac muscarinic K+ channel (KACh) in the cell-attached patch (no agonist in the pipette). The PAF-induced KACh channel activation was blocked by WEB2086, a PAF-receptor inhibitor, indicating that the PAF-receptor mediated the response. PAF-induced activation was prevented by nordihydroguaieretic acid, a lipoxygenase inhibitor, and AA-861, a 5-lipoxygenase inhibitor, but was not affected by indomethacin, a cyclo-oxygenase inhibitor. The PAF-induced KACh channel activity disappeared upon formation of inside-out patch. In this inside-out patch, intracellular GTP alone induced maximal channel reactivation, which was inhibited by GDP-beta S. These results suggest that 5-lipoxygenase metabolites of PAF-released arachidonic acid cause a persistent stimulation of GK but not the KACh channel itself, resulting in a receptor-independent activation of the KACh channel by GTP.

MeSH terms

  • Animals
  • Arachidonic Acids / metabolism*
  • Benzoquinones / pharmacology
  • Cells, Cultured
  • Flavanones*
  • Flavonoids / pharmacology
  • GTP-Binding Proteins / metabolism*
  • Guanosine 5'-O-(3-Thiotriphosphate) / pharmacology
  • Guanosine Triphosphate / pharmacology
  • Guinea Pigs
  • Heart / drug effects*
  • Heart / physiology
  • Heart Atria
  • Indomethacin / pharmacology
  • Lipoxygenase Inhibitors / pharmacology
  • Masoprocol / pharmacology
  • Membrane Potentials / drug effects
  • Myocardium / metabolism*
  • Platelet Activating Factor / pharmacology*
  • Potassium Channels / drug effects
  • Potassium Channels / physiology
  • Virulence Factors, Bordetella / pharmacology


  • Arachidonic Acids
  • Benzoquinones
  • Flavanones
  • Flavonoids
  • Lipoxygenase Inhibitors
  • Platelet Activating Factor
  • Potassium Channels
  • Virulence Factors, Bordetella
  • Guanosine 5'-O-(3-Thiotriphosphate)
  • baicalein
  • Masoprocol
  • 2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone
  • Guanosine Triphosphate
  • GTP-Binding Proteins
  • Indomethacin