Moeller I, Albiston A L, Lew R A, Mendelsohn F A, Chai S Y
Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Victoria, Australia.
J Neurochem. 1999 Jul;73(1):301-8. doi: 10.1046/j.1471-4159.1999.0730301.x.
The AT4 receptor was characterized initially as a specific binding site for angiotensin IV, a C-terminal fragment of the vasoactive peptide angiotensin II. Recently, we found that LVV-hemorphin-7, a fragment of beta globin, is an abundant peptide in the brain and binds to the AT4 receptor with high affinity and specificity. In the neuroblastoma/glioma hybrid cell line, NG108-15, LVV-hemorphin-7 and angiotensin IV competed for 125I-angiotensin IV binding in a biphasic fashion with IC50 values of 1.2 x 10(-10) and 1.1 x 10(-9) M for the high-affinity site, respectively, and 6.7 x 10(-8) and 1.5 x 10(-8) M for the low-affinity site, respectively. Both peptides were internalized rapidly by the cells. However, LVV-hemorphin-7, but not angiotensin IV, elicited a 1.8-fold increase in DNA synthesis in a dose-dependent manner. Furthermore, co-incubation of the cells with an excess of angiotensin IV (10(-6) M) inhibited LVV-hemorphin-7-stimulated DNA synthesis. Therefore, whereas LVV-hemorphin-7 and angiotensin IV were capable of binding to the AT4 receptor, only LVV-hemorphin-7 elicited [3H]thymidine incorporation in NG108-15 cells. In contrast, angiotensin IV behaved as an antagonist. The current finding suggests that LVV-hemorphin-7 is a functional peptide in the central nervous system and in view of its abundance in neural tissue, compared with angiotensin IV, may be of significant physiological importance.
AT4受体最初被鉴定为血管活性肽血管紧张素II的C末端片段血管紧张素IV的特异性结合位点。最近，我们发现β珠蛋白片段LVV-血啡肽-7是大脑中一种丰富的肽，它以高亲和力和特异性与AT4受体结合。在神经母细胞瘤/胶质瘤杂交细胞系NG108-15中，LVV-血啡肽-7和血管紧张素IV以双相方式竞争125I-血管紧张素IV的结合，高亲和力位点的IC50值分别为1.2×10(-10)和1.1×10(-9)M，低亲和力位点的IC50值分别为6.7×10(-8)和1.5×10(-8)M。两种肽都能被细胞迅速内化。然而，LVV-血啡肽-7而非血管紧张素IV能以剂量依赖性方式使DNA合成增加1.8倍。此外，细胞与过量血管紧张素IV(10(-6)M)共同孵育可抑制LVV-血啡肽-7刺激的DNA合成。因此，尽管LVV-血啡肽-7和血管紧张素IV都能与AT4受体结合，但只有LVV-血啡肽-7能引起NG108-15细胞中[3H]胸腺嘧啶核苷掺入。相比之下，血管紧张素IV表现为拮抗剂。目前的发现表明，LVV-血啡肽-7是中枢神经系统中的一种功能性肽，鉴于其在神经组织中的丰富性，与血管紧张素IV相比，可能具有重要的生理意义。
