タナカ　ヨシオ   Tanaka Yoshio   田中　芳夫    所属   東邦大学  薬学部 薬学科    職種   教授
論文種別	原著
言語種別	英語
査読の有無	査読あり
表題	Thromboxane A2 receptor and MaxiK-channel intimate interaction supports channel trans-inhibition independent of G-protein activation.
掲載誌名	正式名：Proceedings of the National Academy of Sciences of the United States of America 略　 称：ProNAS
巻・号・頁	107(44),pp.19096-19101
著者・共著者	Li M, Tanaka Y†, Alioua A, Wu Y, Lu R, Kundu P, Sanchez-Pastor E, Marijic J, Stefani E, Toro L
担当区分	2nd著者
発行年月	2010/11
概要	Large conductance voltage- and calcium-activated potassium channels (MaxiK, BK(Ca)) are well known for sustaining cerebral and coronary arterial tone and for their linkage to vasodilator β-adrenergic receptors. However, how MaxiK channels are linked to counterbalancing vasoconstrictor receptors is unknown. Here, we show that vasopressive thromboxane A2 receptors (TP) can intimately couple with and inhibit MaxiK channels. Activation of the receptor with its agonist trans-inhibits MaxiK independently of G-protein activation. This unconventional mechanism is supported by independent lines of evidence: (i) inhibition of MaxiK current by thromboxane A2 mimetic, U46619, occurs even when G-protein activity is suppressed; (ii) MaxiK and TP physically associate and display a high degree of proximity; and (iii) Förster resonance energy transfer occurs between fluorescently labeled MaxiK and TP, supporting a direct interaction. The molecular mechanism of MaxiK-TP intimate interaction involves the receptor's first intracellular loop and C terminus, and it entails the voltage-sensing conduction cassette of MaxiK channel. Further, physiological evidence of MaxiK-TP physical interaction is given in human coronaries and rat aorta, and by confirming TP role (with antagonist SQ29,548) in the U46619-induced MaxiK inhibition in human coronaries. We propose that vasoconstrictor TP receptor and MaxiK-channel direct interaction facilitates G-protein-independent TP to MaxiK trans-inhibition, which would promote vasoconstriction.
文献番号	20959415