Alpha-adrenergic activation of the muscarinic K+ channel is mediated by arachidonic acid metabolites.
Phenylephrine (10 microM), added in the bathing solution, stimulated the cardiac muscarinic K+ channel (IK.ACh) in the cell-attached patch. The pipette solution contained 10 microM atropine and 100 microM theophylline to block the muscarinic acetylcholine and adenosine receptors, respectively. The channel activation induced by phenylephrine was blocked by prazosin, an alpha 1-antagonist, indicating that alpha 1-adrenergic receptor mediates the response. Phenylephrine-induced activation was prevented by nordihydroguaiaretic acid, a lipoxygenase inhibitor, and AA-861, a 5-lipoxygenase inhibitor, but was not affected by indomethacin, a cyclooxygenase inhibitor. These observations suggest that 5-lipoxygenase metabolites of arachidonic acid may be involved in the alpha-adrenergic activation of IK.ACh.
Kurachi
Y
Y
2nd Department of Internal Medicine, University of Tokyo, Japan.
Ito
H
H
Sugimoto
T
T
Shimizu
T
T
Miki
I
I
Ui
M
M
D000818:Animals; D001091:Arachidonate Lipoxygenases / Q000037:antagonists & inhibitors*; D016718:Arachidonic Acid; D001095:Arachidonic Acids / Q000378:metabolism*; D016861:Cyclooxygenase Inhibitors; D006168:Guinea Pigs; D066298:In Vitro Techniques; D016859:Lipoxygenase Inhibitors; D009206:Myocardium / Q000166:cytology*; D010656:Phenylephrine / Q000494:pharmacology*; D015221:Potassium Channels / Q000187:drug effects*
D001095:Arachidonic Acids; D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D015221:Potassium Channels; D010656:Phenylephrine; D016718:Arachidonic Acid; D001091:Arachidonate Lipoxygenases