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α_1-肾上腺素受体亚型介导细胞内游离Ca~(2+)增高的信号转导途径

李和旺, 耿秋明, 张幼怡, 韩启德

北京医科大学第三医院血管医学研究所

摘要

本文探讨了α1a，α1b，α1d三种亚型肾上腺素受体（AR）激动时细胞内Ca2＋浓度（[Ca2＋]i）升高的信号转导途径。在稳定表达三亚型α1－AR的HEK293细胞系中，用fura－2方法描记细胞内Ca2＋信号强弱的变化。结果显示，百日咳毒素（PTX）对去甲肾上腺素激动三亚型α1－AR而引起的[Ca2＋]i升高无影响，U-73122和PMA明显抑制[Ca2＋]i升高；CalphoshtinC和PWA过夜预处理可翻转PMA的抑制作用；Forskolin和Rp-cAMPs对α1-AR介导的[Ca2＋]；升高无影响，但Quercetin和Tyrphostin可抑制[Ca2＋]；升高峰值，对平台期幅值则无影响。因此，在HEK293细胞，三亚型α1－AR可通过PTX非敏感G蛋白激活PLG而介导磷酸肌醇-Ca2＋信号系统，PKC磷酸化系统既抑制α1－AR介导的细胞内贮存Ca2＋释放，又抑制细胞外Ca2＋内流；cAMP系统不参与α1－AR介导Ca2＋信号的调节，酪氨酸激酶可能参与这一过程。

关键词： α_1一肾上腺素受体; 受体亚型; G蛋白; 磷脂酶C; 蛋白激酶C; 环-磷酸腺苷; 酪氨酸激酶; fura－2

Cui Hong

First Clinical Institute，China Medical University. Shenyang 110001,Liaoning, China

Abstract

In HEK293 cell lines in which α1a-, α1b- or α1d-adrenoceptor subtypes were stably expressed, fluorescence intensities due to traces of Ca2+ were investigated using fura-2/ AM with the aim of exploring signal transduction pathways of intracellular Ca2+ increase mediated by these receptor subtypes. Pertussis toxin had no effect on [ Ca2+ j, increase mediated by all three subdues of α1-adrenoceptors. However, U-73122 and PMA could inhibited the [ Ca2+ ], increase induced by NE, which was not affected by Foskolin and RP-cAMPs. Pretreatment with calphostin C abolished the [ Ca2+ ], response tO PMA.Quercetin and twhostin inhabited maximal [ Ca2+ ], increase but had no effect on the plateau phase in all the three transfected cells. In the HEK293 cells, the phosphatideCa2+ signalling system mediated by the 3 subtypes of al-AR was brought into play by activation of phospholiphase C via coupling with PIX-insensitive G proteins.

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引用本文：

李和旺, 耿秋明, 张幼怡, 韩启德. α_1-肾上腺素受体亚型介导细胞内游离Ca~(2+)增高的信号转导途径 [J]. 生理学报 1998; 50 (3): .

Cui Hong. . Acta Physiol Sin 1998; 50 (3): (in Chinese with English abstract).