Simultaneous inhibitions of inositol phospholipid breakdown, arachidonic acid release, and histamine secretion in mast cells by islet-activating protein, pertussis toxin. A possible involvement of the toxin-specific substrate in the Ca2+-mobilizing receptor-mediated biosignaling system.
Simultaneous inhibitions of inositol phospholipid breakdown, arachidonic acid release, and histamine secretion in mast cells by islet-activating protein, pertussis toxin. A possible involvement of the toxin-specific substrate in the Ca2+-mobilizing receptor-mediated biosignaling system.
复制标题
胰岛激活蛋白、百日咳毒素同时抑制肥大细胞中的肌醇磷脂分解、花生四烯酸释放和组胺分泌。
DOI：
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发表时间：
1985
影响因子：
4.8
通讯作者：
M. Ui
中科院分区：
文献类型：
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作者：
T. Nakamura;M. Ui
化合物48/80与大鼠肥大细胞孵育后，磷脂酰肌醇4，5-二磷酸瞬间分解，肌醇多磷酸迅速生成，45Ca内流，花生四烯酸主要从磷脂酰胆碱释放，最终导致组胺分泌。细胞暴露于胰岛激活蛋白(IAP)、百日咳毒素2小时后，所有这些从钙激活受体到脱颗粒的信号传递过程都被显著抑制。A23187导致45Ca内流和花生四烯酸和组胺的释放，而不会导致肌醇磷脂的分解。与化合物48/80相比，A23187的作用不因细胞暴露于IAP而改变。肥大细胞匀浆的上清液与IAP的活性成分孵育后，将添加的[α-32P]NAD的ADP-核糖基部分转移到MR=41,000的蛋白质上。IAP催化的ADP-核糖化可被5‘-(3-O-硫代)三磷酸阻止，表明这种IAP底物在性质上类似于参与抑制腺苷环化酶的鸟嘌呤核苷酸调节蛋白(Ni)的阿尔法亚基。IAP底物的ADP核糖化程度通过预先将匀浆供体细胞暴露于更高浓度的IAP而逐渐被阻止。对于所研究的所有IAP敏感过程，毒素的半最大有效浓度为0.2至0.6 ng/ml。因此，在细胞暴露于IAP期间发生的MR=41,000蛋白的ADP核糖化似乎是所观察到的信号抑制的原因。有人认为，镍的α亚基或类似的蛋白质，可能在钙门控之前，介导了钙动员受体产生的信号转导。
Incubation of rat mast cells with compound 48/80 resulted in transient breakdown of phosphatidylinositol 4,5-bisphosphate, rapid generation of inositol polyphosphates, 45Ca inflow, and the arachidonic acid liberation mainly from phosphatidylcholine, eventually leading to histamine secretion. All of these processes of signaling from Ca-mobilizing receptors to degranulation were markedly inhibited by prior 2-h exposure of cells to islet-activating protein (IAP), pertussis toxin. A23187 caused 45Ca inflow and releases of arachidonic acid and histamine without inducing breakdown of inositol phospholipids. The effects of A23187, in contrast to those of compound 48/80, were not altered by the exposure of cells to IAP. Incubation of the supernatant fraction of mast cell homogenates with the active component of IAP caused the transfer of the ADP-ribosyl moiety of added [alpha-32P]NAD to a protein with Mr = 41,000. The IAP-catalyzed ADP-ribosylation of this protein was prevented by guanosine 5'-(3-O-thio)triphosphate, indicating that this IAP substrate resembles, in character, the alpha-subunit of the guanine nucleotide regulatory protein (Ni) involved in inhibition of adenylate cyclase. The degree of ADP-ribosylation of this IAP substrate was prevented progressively by pre-exposure of the homogenate-donor cells to increasing concentrations of IAP. The half-maximally effective concentrations of the toxin were 0.2 to 0.6 ng/ml for all the IAP-sensitive processes studied. Thus, the ADP-ribosylation of the Mr = 41,000 protein occurring during exposure of cells to IAP appears to be responsible for the inhibition of signaling observed. It is proposed that the alpha-subunit of Ni, or a like protein, mediates signal transduction arising from Ca-mobilizing receptors, probably prior to Ca2+ gating.