Sphingosylphosphorylcholine Is a Novel Messenger for Rho-Kinase–Mediated Ca2+Sensitization in the Bovine Cerebral ArteryUnimportant Role for Protein Kinase C
作者:
Satoshi Shirao,
Shiro Kashiwagi,
Masafumi Sato,
Saori Miwa,
Fumiaki Nakao,
Tetsu Kurokawa,
Natsuko Todoroki-Ikeda,
Kimiko Mogami,
Yoichi Mizukami,
Shinichi Kuriyama,
Kyousuke Haze,
Michiyasu Suzuki,
Sei Kobayashi,
期刊:
Circulation Research: Journal of the American Heart Association
(OVID Available online 2002)
卷期:
Volume 91,
issue 2
页码: 112-119
ISSN:0009-7330
年代: 2002
出版商: OVID
关键词: vasospasm;sphingolipid;protein kinase C;Rho-kinase;membrane permeabilization
数据来源: OVID
摘要:
Although recent investigations have suggested that a Rho-kinase–mediated Ca2+sensitization of vascular smooth muscle contraction plays a critical role in the pathogenesis of cerebral and coronary vasospasm, the upstream of this signal transduction has not been elucidated. In addition, the involvement of protein kinase C (PKC) may also be related to cerebral vasospasm. We recently reported that sphingosylphosphorylcholine (SPC), a sphingolipid, induces Rho-kinase–mediated Ca2+sensitization in pig coronary arteries. The purpose of this present study was to examine the possible mediation of SPC in Ca2+sensitization of the bovine middle cerebral artery (MCA) and the relation to signal transduction pathways mediated by Rho-kinase and PKC. In intact MCA, SPC induced a concentration-dependent (EC50=3.0 &mgr;mol/L) contraction, without [Ca2+]ielevation. In membrane-permeabilized MCA, SPC induced Ca2+sensitization even in the absence of added GTP, which is required for activation of G-proteins coupled to membrane receptors. The SPC-induced Ca2+sensitization was blocked by a Rho-kinase inhibitor (Y-27632) and a dominant-negative Rho-kinase, but not by a pseudosubstrate peptide for conventional PKC, which abolished the Ca2+-independent contraction induced by phorbol ester. In contrast, phorbol ester–induced Ca2+sensitization was resistant to a Rho-kinase inhibitor and a dominant-negative Rho-kinase. In primary cultured vascular smooth muscle cells, SPC induced the translocation of cytosolic Rho-kinase to the cell membrane. We propose that SPC is a novel messenger for Rho-kinase–mediated Ca2+sensitization of cerebral arterial smooth muscle and, therefore, may play a pivotal role in the pathogenesis of abnormal contraction of the cerebral artery such as vasospasm. The SPC/Rho-kinase pathway functions independently of the PKC pathway.
点击下载:
PDF
(174KB)
返 回