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.
This is a preview of subscription content, log in via an institution to check access.
References
Axelrod J, Burch RM, Jelsema CL (1988) Receptor mediated activation of phospholipase A2 via GTP-binding proteins: arachidonic acid and its metabolites as second messengers. Trends Neurosci. 11: 117–123
Hamill OP, Marty A, Neher E, Sakmann B, Sigworth FJ (1981) Improved patch-clamp techniques for high-resolution current recordings from cells and cell-free membrane patches. Pflügers Arch 391: 85–100
Kurachi Y, Nakajima T, Sugimoto T (1986) On the mechanism of activation of muscarinic K+ channels by adenosine in isolated atrial cells: involvement of GTP-binding proteins. Pflügers Arch 407: 264–274
Kurachi Y, Ito H, Sugimoto T, Shimizu T, Miki I, Ui M (1989) Arachidonic acid metabolites as intracellular modulators of G protein-gated cardiac K+ channel. Nature 337: 555–557
Logothetis DE, Kurachi Y, Galper J, Neer EJ, Clapham DE (1987) The βγ subunits of GTP-binding proteins activate the muscarinic K+ channel in heart. Nature 325: 321–326
Needleman P, Turk J, Jakschik BA, Morrison AR, Lefkowith JB (1986) Arachidonic acid metabolism. Ann Rev Biochem 55: 69–102
Sekiya K, Okuda H (1982) Selective inhibition of platelet lipoxygenase by baicalein. Biochem Biophys Res Com 105: 1090–1095
Yoshimoto T, Yokoyama C, Ochi K Yamamoto S, Maki Y, Ashida Y, Terano S, Shiraishi M (1982) 2, 3.5-trimethyl-1-6-(12-hydroxy-5,10-dodecadiynyl)-1,4-benzoquinone (AA-861), a selective inhibitor of the 5-lipoxygenase reaction and the biosynthesis of slow-reacting substance of anaphylaxis. Biochem Biophys Acta 713: 470–473
Author information
Authors and Affiliations
Additional information
On leave from Kyowa Hakko Kogyo Co., Pharmaceutical Research Laboratories; Nagaizumi-cho, Sunto-gun, Shizuoka 411, Japan
Rights and permissions
About this article
Cite this article
Kurachi, Y., Ito, H., Sugimoto, T. et al. α-Adrenergic activation of the muscarinic K+ channel is mediated by arachidonic acid metabolites. Pflugers Arch. 414, 102–104 (1989). https://doi.org/10.1007/BF00585635
Received:
Accepted:
Issue Date:
DOI: https://doi.org/10.1007/BF00585635