Abstract
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
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Animals
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Arachidonic Acids / metabolism*
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Benzoquinones / pharmacology
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Cells, Cultured
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Flavanones*
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Flavonoids / pharmacology
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GTP-Binding Proteins / metabolism*
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Guanosine 5'-O-(3-Thiotriphosphate) / pharmacology
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Guanosine Triphosphate / pharmacology
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Guinea Pigs
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Heart / drug effects*
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Heart / physiology
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Heart Atria
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Indomethacin / pharmacology
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Lipoxygenase Inhibitors / pharmacology
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Masoprocol / pharmacology
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Membrane Potentials / drug effects
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Myocardium / metabolism*
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Platelet Activating Factor / pharmacology*
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Potassium Channels / drug effects
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Potassium Channels / physiology
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Virulence Factors, Bordetella / pharmacology
Substances
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Arachidonic Acids
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Benzoquinones
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Flavanones
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Flavonoids
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Lipoxygenase Inhibitors
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Platelet Activating Factor
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Potassium Channels
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Virulence Factors, Bordetella
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Guanosine 5'-O-(3-Thiotriphosphate)
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baicalein
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Masoprocol
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2,3,5-trimethyl-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone
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Guanosine Triphosphate
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GTP-Binding Proteins
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Indomethacin