CLONING BY FUNCTIONAL EXPRESSION OF PLATELET-ACTIVATING-FACTOR RECEPTOR FROM GUINEA-PIG LUNG

CLONING BY FUNCTIONAL EXPRESSION OF PLATELET-ACTIVATING-FACTOR RECEPTOR FROM GUINEA-PIG LUNG
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DOI:
10.1038/349342a0
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发表时间:
1991-01-24
期刊:
影响因子:
64.8
通讯作者:
SHIMIZU, T
SHIMIZU, T
中科院分区:
综合性期刊1区
文献类型:
--
作者:
HONDA, Z;NAKAMURA, M;SHIMIZU, T

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血小板活化因子(PAF)是一种独特的磷脂介质,具有强烈的促炎、平滑肌收缩和降压活性,在哮喘的发病机制、内毒素和过敏性休克1-3的致死性中起关键作用。尽管如此,对PAF受体的分子特性和相关的信号转导系统知之甚少。尽管一些证据表明PAF受体的激活通过G蛋白(S)4,5刺激磷脂酶C和随后的三磷酸肌醇的形成,但是PAF受体和钙通道被报道有密切的关系2,6。作为第一个克隆脂质金盏样受体的方法,我们分离了PAF受体的互补DNA。我们的策略涉及非洲爪哇卵母细胞的基因表达和PAF诱导反应的电生理检测。序列分析表明,该受体属于G蛋白偶联受体超家族。
PLATELET-activating factor (PAF), a unique phospholipid mediator, possesses potent proinflammatory, smooth-muscle contractile and hypotensive activities, and appears to be crucial in the pathogenesis of bronchial asthma and in the lethality of endotoxin and anaphylactic shock1-3. Despite this, little is known of the molecular properties of the PAF receptor and related signal transduction systems. Although several lines of evidence suggest that activation of the PAF receptor stimulates phospholipase C and subsequent inositol trisphosphate formation through G protein(s)4,5, the PAF receptor and calcium channel are reported to show a close relation2,6. As a first approach to cloning lipid autacoid receptors, we have isolated complementary DNA for the PAF receptors. Our strategy involved gene expression in Xenopus laevis oocytes and electrophysiological detection of PAF-induced responses. Sequence analysis indicates that the receptor belongs to the superfamily of G protein-coupled receptors.