Smith R D, Corps A N, Hadfield K M, Vaughan T J, Brown K D
Department of Cellular Physiology, Babraham Institute, Cambridge, U.K.
Biochem J. 1994 Sep 15;302 ( Pt 3)(Pt 3):791-800. doi: 10.1042/bj3020791.
Proliferation of the rat intestinal epithelial cell-line, RIE-1, has previously been shown to be stimulated by certain polypeptide growth factors acting via receptors that possess intrinsic tyrosine kinase activity. In this study, we show that the octapeptide hormone angiotensin II (AII), apparently acting through the AT1 G-protein-coupled receptor, is also a mitogen for RIE-1 cells. Maximal stimulation of DNA synthesis and cellular proliferation occurred at an AII concentration of 10-100 nM, with half-maximal stimulation at 1 nM. The mitogenic response to AII was completely inhibited by the AT1 angiotensin-receptor antagonist, DuP753, but not by the AT2-receptor antagonist, PD123319. The early signalling responses activated by AII in RIE-1 cells include increased production of inositol phosphates, a transient increase in the intracellular concentration of free calcium, an activation of protein kinase C, and a rapid change in the pattern of cellular protein-tyrosine phosphorylation. These results implicate an activation of the inositol lipid signalling pathway via the AT1 receptor subtype in the AII-stimulated mitogenic response of this normal epithelial cell line.
大鼠肠上皮细胞系RIE-1的增殖先前已被证明可受某些通过具有内在酪氨酸激酶活性的受体起作用的多肽生长因子刺激。在本研究中，我们发现八肽激素血管紧张素II（AII）显然通过AT1 G蛋白偶联受体起作用，它也是RIE-1细胞的促有丝分裂原。在AII浓度为10 - 100 nM时，DNA合成和细胞增殖受到最大刺激，半最大刺激浓度为1 nM。对AII的促有丝分裂反应被AT1血管紧张素受体拮抗剂DuP753完全抑制，但不受AT2受体拮抗剂PD123319抑制。AII在RIE-1细胞中激活的早期信号反应包括肌醇磷酸产量增加、细胞内游离钙浓度短暂升高、蛋白激酶C激活以及细胞蛋白酪氨酸磷酸化模式的快速变化。这些结果表明，在这种正常上皮细胞系的AII刺激的促有丝分裂反应中，通过AT1受体亚型激活了肌醇脂质信号通路。
