RECOMBINANT BOVINE NEUROKININ-2 RECEPTOR STABLY EXPRESSED IN CHINESE-HAMSTER OVARY CELLS COUPLES TO MULTIPLE SIGNAL TRANSDUCTION PATHWAYS
RECOMBINANT BOVINE NEUROKININ-2 RECEPTOR STABLY EXPRESSED IN CHINESE-HAMSTER OVARY CELLS COUPLES TO MULTIPLE SIGNAL TRANSDUCTION PATHWAYS
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DOI：
10.1091/mbc.2.10.767
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发表时间：
1991-10-01
期刊：
影响因子：
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通讯作者：
ARKINSTALL, SJ
中科院分区：
文献类型：
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作者：
EISTETTER, HR;CHURCH, DJ;ARKINSTALL, SJ
神经激肽是一个广泛分布的神经肽家族，通过三种不同的受体亚型：NK-1、NK-2和NK-3介导广泛的生理作用。我们研究了在中国仓鼠卵巢细胞中稳定表达的重组牛NK-2受体控制下的一些第二信使和细胞过程。在该系统中，NK-2受体显示其预期的药理学特性，并且生理激动剂神经激肽A刺激几种细胞反应。这些包括1）瞬时的肌醇1，4，5-三磷酸（IP 3）形成和Ca 2+动员，2）增加的花生四烯酸和前列腺素E2（PGE 2）的输出，3）增强的环AMP（cAMP）产生，4）增加的从头DNA合成，和5）“立即早期”基因c-fos和c-jun的诱导。虽然NK-2受体介导的IP 3形成涉及百日咳毒素不敏感的G蛋白的激活，cAMP产生的增加主要是继发性反应，并且至少部分归因于内源性产生的类二十烷酸，特别是PGE 2的自分泌刺激。这是第一次证明，一个单一的重组神经激肽受体亚型可以调节，直接或间接，多个信号转导通路，并建议在生理条件下的神经激肽行动的几个潜在的重要介质。
Neurokinins are a family of neuropeptides with widespread distribution mediating a broad spectrum of physiological actions through three distinct receptor subtypes: NK-1, NK-2, and NK-3. We investigated some of the second messenger and cellular processes under control by the recombinant bovine NK-2 receptor stably expressed in Chinese hamster ovary cells. In this system the NK-2 receptor displays its expected pharmacological characteristics, and the physiological agonist neurokinin A stimulates several cellular responses. These include 1) transient inositol 1,4,5-trisphosphate (IP3) formation and Ca2+ mobilization, 2) increased out put of arachidonic acid and prostaglandin E2 (PGE2), 3) enhanced cyclic AMP (cAMP) generation, 4) increased de novo DNA synthesis, and 5) an induction of the "immediate early" genes c-fos and c-jun. Although NK-2 receptor-mediated IP3 formation involves activation of a pertussis toxin-insensitive G-protein, increased cAMP production is largely a secondary response and can be at least partially attributed to autocrine stimulation by endogenously generated eicosanoids, particularly PGE2. This is the first demonstration that a single recombinant neurokinin receptor subtype can regulate, either directly or indirectly, multiple signal transduction pathways and suggests several potential important mediators of neurokinin actions under physiological conditions.