Homologous desensitization of thromboxane A2 receptor in 1321N1 human astrocytoma cells.
Homologous desensitization of thromboxane A2 receptor in 1321N1 human astrocytoma cells.
复制标题
1321N1 人星形细胞瘤细胞中血栓素 A2 受体的同源脱敏。
DOI：
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发表时间：
1996
影响因子：
3.5
通讯作者：
Y. Ohizumi
中科院分区：
文献类型：
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作者：
K. Sakai;N. Nakahata;H. Ono;T. Yamamoto;Y. Ohizumi
在1321 N1人星形细胞瘤细胞中研究了调节血栓素A2（TXA 2）反应的脱敏机制。将细胞暴露于浓度为1 μ M的稳定的TXA 2受体激动剂9，11-表硫代-11，12-甲硫氨烷A2（STA 2）30至45分钟，导致随后STA 2刺激的磷酸肌醇水解和Ca 2+动员减少约50%。然而，暴露于STA 2 0至5小时不改变[3 H] SQ 29548，TXA 2受体拮抗剂的结合。STA 2作用30 min后，细胞对GT3的激活作用减弱，对[3 H] SQ 29548结合的抑制作用消失，提示短期内TXA 2受体的脱敏可能是G蛋白-受体解偶联的结果。STA 2诱导的脱敏是特异性的TXA 2受体和同源的，因为SQ 29548抑制脱敏和STA 2预处理不影响卡巴胆碱，毒蕈碱胆碱能受体激动剂的反应。暴露于STA 2 24小时减少[3 H] SQ 29548结合位点至对照的20 - 30%，并消除STA 2刺激的磷酸肌醇水解，表明长期脱敏可能诱导TXA 2受体的下调。然而，暴露于STA 2 1至24小时没有改变TXA 2受体mRNA的水平。这些结果表明，同源脱敏的TXA 2受体在人星形细胞瘤细胞可分为两个阶段，早期涉及解偶联的G-蛋白的受体和晚期涉及细胞中的受体的损失。mRNA水平可能不受TXA 2受体刺激的控制。
The desensitization mechanisms that regulate the response to thromboxane A2 (TXA2) were investigated in 1321N1 human astrocytoma cells. Exposure of the cells to 9,11-epithio-11, 12-methanothromboxane A2 (STA2), a stable TXA2 receptor agonist, at a concentration of 1 microM for 30 to 45 min resulted in about a 50% decrease in subsequent STA2-stimulated phosphoinositide hydrolysis and Ca2+ mobilization. However, exposure to STA2 for 0 to 5 hr did not change the binding of [3H]SQ29548, a TXA2 receptor antagonist. Because STA2-induced GTPase activation decreased and the GTP sensitivity in inhibition of [3H]SQ29548 binding by STA2 disappeared after the cells had been exposed to STA2 for 30 min, the TXA2 receptor desensitization during the short-term might result from G-protein-receptor uncoupling. STA2-induced desensitization was specific for the TXA2 receptor and homologous, because SQ29548 suppressed the desensitization and STA2 pretreatment did not affect the response to carbachol, a muscarinic cholinergic receptor agonist. Exposure to STA2 for 24 hr decreased [3H]SQ29548 binding sites to 20 to 30% of control and abolished STA2-stimulated phosphoinositide hydrolysis, indicating that long-term desensitization might induce down-regulation of the TXA2 receptor. However, exposure to STA2 for 1 to 24 hr did not change the level of TXA2 receptor mRNA. These results show that homologous desensitization of the TXA2 receptor in human astrocytoma cells can be divided into two stages; the early stage involves uncoupling of receptors from G-proteins and the late stage involves a loss of receptors in cells. The mRNA levels may not be controlled by stimulation of the TXA2 receptor.