Novotný J, Krůsek J, Drmota T, Svoboda P
Institute of Physiology, Academy of Sciences of the Czech Republic, Prague.
Life Sci. 1999;65(9):889-900. doi: 10.1016/s0024-3205(99)00319-7.
Doubly transfected human embryonal kidney cells (clone E2M11 of the HEK 293 cell line) expressing both thyrotropin-releasing hormone (TRH) receptors and G11alpha protein in high amounts were used to analyze the desensitization phenomenon of the Ca2+-mobilizing pathway. Quite unexpectedly, we did not observe any significant desensitization of the [Ca2+]i response to TRH in these cells after repeated or prolonged incubation with the hormone (up to 5 h). Under the same conditions, the TRH-induced [Ca2+]i response was completely desensitized in the parent cell line (293-E2 cels) expressing TRH receptors alone. In both cell lines, inositol phosphate response was desensitized after TRH exposure, although basal levels of inositol phospates in TRH-pretreated cells were much higher than in "naive" TRH-unexposed cells. These data suggest a significant role of the G protein G11alpha in desensitization of the Ca2+-mobilizing pathway occuring after repeated or long-term exposure of target cells to TRH-receptor agonists.
使用大量表达促甲状腺激素释放激素（TRH）受体和G11α蛋白的双转染人胚肾细胞（HEK 293细胞系的克隆E2M11）来分析Ca2+动员途径的脱敏现象。非常出乎意料的是，在用该激素反复或长时间孵育（长达5小时）后，我们在这些细胞中未观察到[Ca2+]i对TRH的反应有任何明显的脱敏现象。在相同条件下，单独表达TRH受体的亲本细胞系（293-E2细胞）中，TRH诱导的[Ca2+]i反应完全脱敏。在这两种细胞系中，TRH暴露后肌醇磷酸反应均脱敏，尽管经TRH预处理的细胞中肌醇磷酸的基础水平比未暴露于TRH的“未处理”细胞高得多。这些数据表明，在靶细胞反复或长期暴露于TRH受体激动剂后发生的Ca2+动员途径脱敏中，G蛋白G11α起重要作用。
