?-Adrenergic activation of the muscarinic K+ channel is mediated by arachidonic acid metabolites

Abstract
Phenylephrine (10 μM), added in the bathing solution, stimulated the cardiac muscarinic K+ channel (IK.ACh) in the cell-attached patch. The pipette solution contained 10 μM atropine and 100 μM theophylline to block the muscarinic acetylcholine and adenosine receptors, respectively. The channel activation induced by phenylephrine was blocked by prazosin, an α1-antagonist, indicating that α1-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 α-adrenergic activation of IK.ACh.