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首页> 外文期刊>Hypertension: An Official Journal of the American Heart Association >G-Protein-Coupled Receptor MrgD Is a Receptor for Angiotensin-(1-7) Involving Adenylyl Cyclase, cAMP, and Phosphokinase A
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G-Protein-Coupled Receptor MrgD Is a Receptor for Angiotensin-(1-7) Involving Adenylyl Cyclase, cAMP, and Phosphokinase A

机译：G蛋白偶联受体MrgD是血管紧张素-（1-7）涉及腺苷酸环化酶，cAMP和磷酸激酶A的受体。

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Angiotensin (Ang)-(1-7) has cardiovascular protective effects and is the opponent of the often detrimental Ang II within the renin-angiotensin system. Although it is well accepted that the G-protein-coupled receptor Mas is a receptor for the heptapeptide, the lack in knowing initial signaling molecules stimulated by Ang-(1-7) prevented definitive characterization of ligand/receptor pharmacology as well as identification of further hypothesized receptors for the heptapeptide. The study aimed to identify a second messenger stimulated by Ang-(1-7) allowing confirmation as well as discovery of the heptapeptide's receptors. Ang-(1-7) elevates cAMP concentration in primary cells, such as endothelial or mesangial cells. Using cAMP as readout in receptor-transfected human embryonic kidney (HEK293) cells, we provided pharmacological proof that Mas is a functional receptor for Ang-(1-7). Moreover, we identified the G-protein-coupled receptor MrgD as a second receptor for Ang-(1-7). Consequently, the heptapeptide failed to increase cAMP concentration in primary mesangial cells with genetic deficiency in both Mas and MrgD. Mice deficient in MrgD showed an impaired hemodynamic response after Ang-(1-7) administration. Furthermore, we excluded the Ang II type 2 receptor as a receptor for the heptapeptide but discovered that the Ang II type 2 blocker PD123319 can also block Mas and MrgD receptors. Our results lead to an expansion and partial revision of the renin-angiotensin system, by identifying a second receptor for Ang-(1-7), by excluding Ang II type 2 as a receptor for the heptapeptide, and by enforcing the revisit of such publications which concluded Ang II type 2 function by only using PD123319.
机译：血管紧张素（Ang）-（1-7）具有心血管保护作用，并且是肾素-血管紧张素系统中经常有害的Ang II的对手。尽管公认的G蛋白偶联受体Mas是七肽的受体，但由于缺乏对Ang-（1-7）刺激的初始信号分子的了解，因此无法确定配体/受体药理学的确切特征以及进一步假设的七肽受体。该研究旨在确定由Ang-（1-7）刺激的第二个信使，该信使可以确认和发现七肽的受体。 Ang-（1-7）可提高原代细胞（如内皮细胞或系膜细胞）中的cAMP浓度。使用cAMP作为受体转染的人类胚胎肾（HEK293）细胞中的读数，我们提供了药理学证据，证明Mas是Ang-（1-7）的功能性受体。此外，我们确定了G蛋白偶联受体MrgD作为Ang-（1-7）的第二受体。因此，七肽未能增加Mas和MrgD均具有遗传缺陷的原代系膜细胞中的cAMP浓度。缺乏MrgD的小鼠在Ang-（1-7）给药后显示出血液动力学反应受损。此外，我们排除了Ang II 2型受体作为七肽的受体，但发现Ang II 2型阻断剂PD123319也可以阻断Mas和MrgD受体。我们的结果通过确定Ang-（1-7）的第二种受体，排除Ang II 2类作为七肽的受体并强制重新审视Ang-（1-7）的第二种受体，从而导致肾素-血管紧张素系统的扩展和部分修订。仅使用PD123319即可得出Ang II 2型功能的出版物。

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