Direct linkage of three tachykinin receptors to stimulation of both phosphatidylinositol hydrolysis and cyclic AMP cascades in transfected Chinese hamster ovary cells.
Direct linkage of three tachykinin receptors to stimulation of both phosphatidylinositol hydrolysis and cyclic AMP cascades in transfected Chinese hamster ovary cells.
复制标题
DOI：
10.1016/s0021-9258(18)45898-x
复制
发表时间：
1992-02
期刊：
影响因子：
--
通讯作者：
Y. Nakajima;K. Tsuchida;M. Negishi;Saori Ito;Shigetada Nakanishi
中科院分区：
文献类型：
--
作者：
Y. Nakajima;K. Tsuchida;M. Negishi;Saori Ito;Shigetada Nakanishi
哺乳动物速激肽系统由P物质、K物质和神经介素K三个不同的多肽组成，并具有三个相应的受体。在这项研究中，我们通过在中国仓鼠卵巢细胞中转染和稳定表达单个速激肽受体cDNA来检测这些受体的细胞内信号转导。这三种受体在速激肽的相互作用下，对磷脂酰肌醇(PI)的水解和环状AMP的形成都表现出快速而显著的刺激作用。这三种受体与磷脂酶C和腺苷环化酶直接相连的证据是，速激肽与GTP一起激活了来自速激肽受体表达细胞的膜制剂中的这些酶的活性。在受体表达细胞及其膜制剂中，刺激环状AMP形成的效率低于PI水解法(有效多肽浓度相差约1个数量级)。然而，在表达受体的细胞和它们的膜制品中都诱导了PI水解和环状AMP形成的刺激反应，这与每种受体亚型的速激肽结合选择性完全一致。这项研究明确地证明速激肽受体有可能直接与磷脂酶C和腺苷环化酶偶联，并刺激PI的水解和环状AMP的形成。
The mammalian tachykinin system consists of three distinct peptides, substance P, substance K, and neuromedin K, and possesses three corresponding receptors. In this investigation we examined intracellular signal transduction of the individual tachykinin receptors by transfection and stable expression of these receptor cDNAs in Chinese hamster ovary cells. The three receptors commonly showed a rapid and marked stimulation in both phosphatidylinositol (PI) hydrolysis and cyclic AMP formation in response to tachykinin interaction. Direct linkage of the three receptors to both phospholipase C and adenylate cyclase was evidenced by the finding that tachykinin, added together with GTP, activated these enzyme activities in membrane preparations derived from tachykinin receptor-expressing cells. The stimulation of cyclic AMP formation was less efficient than that of PI hydrolysis in receptor-expressing cells as well as their membrane preparations (about 1 order of magnitude difference in the effective peptide concentrations). However, the stimulatory responses of the PI hydrolysis and cyclic AMP formation in both receptor-expressing cells and their membrane preparations were induced in complete agreement with the tachykinin binding selectivity of each subtype of the receptors. This investigation demonstrated unequivocally that the tachykinin receptors have the potential to couple directly to both phospholipase C and adenylate cyclase and to stimulate PI hydrolysis and cyclic AMP formation.