α1-肾上腺素受体亚型介导细胞内游离Ca2+增高的信号转导途径

本文探讨了α１ａ,α１ｂ,α１ｄ三种亚型肾上腺素受体激动时细胞内Ｃａ６２＋浓度升高的信号转导途径。在稳定表达三亚型α１－ＡＲ的ＨＥＫ２９３细胞２系中,用ｆｕｒａ－２方法细胞内Ｃａ＾２＋信号强弱的变化。结果显示,百日咳毒素对去甲肾上腺素激动三亚型α１－ＡＲ而引起的「Ｃａ＾２＋」ｉ升高无影响,Ｕ－７３１２２和ＰＭＡ明显抑制「Ｃａ＾２＋」ｉ升高．

Pathways of signal transduction of intracellular Ca2+ increase mediated by three subtypes of alpha 1-adrenoceptor in HEK293 cells

In HEK293 cell lines in which alpha 1a-, alpha 1b- or alpha 1d-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+]i increase mediated by all three subtypes of alpha 1-adrenoceptors. However, U-73122 and PMA could inhibited the Ca2+]i increase induced by NE, which was not affected by Foskolin and Rp-cAMPs. Pretreatment with calphostin C abolished the Ca2+]i response to PMA. Quercetin and tyrphostin inhibited maximal Ca2+]i increase but had no effect on the plateau phase in all the three transfected cells. In the HEK293 cells, the phosphatide-Ca2+ signalling system mediated by the 3 subtypes of alpha 1-AR was brought into play by activation of phospholiphase C via coupling with PTX-insensitive G proteins. PKC system inhibited both mobilization of internal Ca2+ stores and the Ca2+ influx across the plasma membrane. Tyrosine kinase, but not cAMP system, might participate in such Ca2+ signalling.