Platelet‐activating factor activates cardiac GK via arachidonic acid metabolites

FEBS Letters

Sugimoto, Tsuneaki¹  Nakajima, Toshiaki¹  Kurachi, Yoshihisa² 

[1] The 2nd Department of Internal Medicine, Faculty of Medicine, University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113, Japan;Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic, Mayo Foundation, Rochester, MN 55905, USA

关键词: Platelet-activating factor;    Arachidonic acid;    Lipoxygenase;    Cardiac cell;    Potassium channel;    GTP-binding protein;   

DOI  :  10.1016/0014-5793(91)81079-N

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Platelet-activating factor (PAF), added to the bathing solution, stimulated the cardiac muscarinic K⁺ channel (K_ACh) in the cell-attached patch (no agonist in the pipette). The PAF-induced K_ACh 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 K_ACh, 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-βS. These results suggest that 5-lipoxygenase metabolites of PAF-released arachidonic acid cause a persistent stimulation of G_K but not the K_ACh channel itself, resulting in a receptor-independent activation of the K_ACh channel by GTP.

【 授权许可】

Unknown