Angiotensin metabolites can stimulate receptors of the Mas-related genes family
Angiotensin metabolites can stimulate receptors of the Mas-related genes family
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DOI：
10.1007/s11010-008-9884-4
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发表时间：
2008-12-01
影响因子：
4.3
通讯作者：
Walther, Thomas
中科院分区：
文献类型：
--
作者：
Gembardt, Florian;Grajewski, Sonja;Walther, Thomas
Mas原癌基因编码G蛋白偶联受体，我们也通过使用特异性血管紧张素-（1-7）拮抗剂A-779鉴定，其与血管紧张素（Ang）II代谢物Ang-（1-7）的细胞内信号传导相关。近年来，已鉴定出编码Mrg受体家族的Mas相关基因（Mrg）。所有家族成员与Mas具有高度序列同源性。大多数是孤儿受体。为了证明Mrg受体与Mas的结构相似性是否使它们成为Ang-（1-7）或其他Ang代谢物的潜在受体，我们用各种Mrg受体转染COS或HEK 293细胞，并通过记录用Ang II、Ang III、Ang IV和Ang-（1-7）刺激后的血清反应因子（SRF）活化来研究花生四烯酸（AA）释放和转录活化。所研究的受体均未通过SRF激活转录。在对照载体转染的COS细胞中，Ang-（1-7）刺激AA释放，表明存在内源性受体（A-779敏感性）。虽然没有Mas那么明显，但六种研究的受体中的两种（MrgD，MRG）在用Ang-（1-7）刺激后启动了显著的AA释放。有趣的是，Mas、MrgD和MRG介导的Ang IV刺激的AA释放对于Mas最高。而Ang III激活Mas和MrgX 2，Ang II通过Mas和MRG刺激AA释放。因此，我们鉴定了Mrg家族的其他受体对Ang-（1-7）刺激的应答。此外，我们首先描述了AT（1）非依赖性的直接Ang IV信号传导，并表明Ang II和Ang III不依赖于其特异性受体AT（1）和AT（2）介导信号传导，由此受体特异性不同。
The Mas protooncogene encodes a G protein-coupled receptor, we identified, also by using the specific angiotensin-(1-7) antagonist A-779, to be associated with intracellular signaling of the angiotensin (Ang) II metabolite Ang-(1-7). Recently, Mas-related genes (Mrg) have been identified coding for the Mrg-receptor family. All family members share high sequence homology to Mas. Most of them are orphan receptors. To proof whether structure similarities of the Mrg receptors with Mas turn them into potential receptors for Ang-(1-7) or other Ang metabolites, we transfected COS or HEK293 cells with an assortment of Mrg receptors and investigated arachidonic acid (AA) release and transcriptional activation by recording serum response factor (SRF) activation after stimulation with Ang II, Ang III, Ang IV, and Ang-(1-7). None of the investigated receptors activated transcription via SRF. Ang-(1-7) stimulated AA release already in control vector-transfected COS cells, indicating the existence of an endogenous receptor (A-779 sensitive). Though less pronounced than for Mas, two of the six studied receptors (MrgD, MRG) initiated significant AA release after stimulation with Ang-(1-7). Interestingly, Mas, MrgD, and MRG mediated Ang IV-stimulated AA release that was highest for Mas. While Ang III activated Mas and MrgX2, Ang II stimulated AA release via Mas and MRG. Thus, we identified other receptors of the Mrg family to respond on Ang-(1-7) stimulation. Furthermore, we describe first an AT(1)-independent direct Ang IV signaling and show that Ang II and Ang III mediate signaling independent of their specific receptors AT(1) and AT(2), whereby the receptor specificity differs.