Larsson C, Simonsson P
Department of Psychiatry and Neurochemistry, Lund University, Sweden.
Neurosci Lett. 1993 Feb 19;150(2):141-4. doi: 10.1016/0304-3940(93)90521-l.
In this study, the desensitization of acetylcholine-induced inositol 1,4,5-trisphosphate [I(1,4,5)P3] formation, upon short-time prestimulations, was investigated in cultures of human neuroblastoma SH-SY5Y cells. Four repeated stimulations for 10 seconds with 10 microM acetylcholine were necessary to induce a desensitization of the I(1,4,5)P3 formation. The desensitization was observed 4 hours after the initiation of repetitive stimulations. The same effect was obtained by a single prestimulation with 1 mM acetylcholine. Preincubation of the cells with phorbol 12-myristate 13-acetate (PMA) markedly down-regulated the acetylcholine-induced I(1,4,5)P3 formation. However, the protein kinase C (PKC) inhibitors H7 and staurosporine did not influence the desensitization induced by four repeated stimulations with 20 microM acetylcholine. These results indicate that the signal transduction can be desensitized following repeated stimulations with sub-maximal concentrations of receptor agonist and although activation of PKC can induce the same down-regulation, PKC is most likely not involved in the desensitization induced by repetitive acetylcholine-stimulations.
在本研究中，我们在人神经母细胞瘤SH-SY5Y细胞培养物中研究了在短时间预刺激后乙酰胆碱诱导的肌醇1,4,5-三磷酸[I(1,4,5)P3]生成的脱敏作用。用10微摩尔乙酰胆碱进行四次10秒的重复刺激对于诱导I(1,4,5)P3生成的脱敏是必要的。在重复刺激开始4小时后观察到脱敏现象。用1毫摩尔乙酰胆碱进行一次预刺激也能获得相同的效果。用佛波醇12-肉豆蔻酸酯13-乙酸酯（PMA）对细胞进行预孵育可显著下调乙酰胆碱诱导的I(1,4,5)P3生成。然而，蛋白激酶C（PKC）抑制剂H7和星形孢菌素并不影响用20微摩尔乙酰胆碱进行四次重复刺激所诱导的脱敏作用。这些结果表明，用亚最大浓度的受体激动剂进行重复刺激后信号转导可发生脱敏，尽管PKC的激活可诱导相同的下调作用，但PKC很可能不参与重复乙酰胆碱刺激所诱导的脱敏作用。
