Molecular Cloning and Expression of the Gene Encoding Human Angiotensin II Type 2 Receptor

Tsuzuki, Satoshi; Ichiki, Toshihiro; Nakakubo, Hiroshi; Kitami, Yutaka; Guo, Deng Fu; Shirai, Heigoro; Inagami, Tadashi

doi:10.1006/bbrc.1994.1613

Cited by 102 publications

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“…The present study suggests that the AT, gene is present in a single locus in the sheep, and demonstrates a high level of homology between the sheep AT, partial cDNA sequence and corresponding AT, cDNA sequences from other species (22,23,29,30). In addition, we have shown that the expression of AT, receptor mRNA in fetal sheep kidney is high during the second trimester of gestation and decreases rapidly thereafter.…”

Section: Discussionsupporting

confidence: 66%

Differential Gene Expression and Regulation of Renal Angiotensin II Receptor Subtypes (AT1 and AT2) during Fetal Life in Sheep

et al. 1995

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Previous studies have shown that angiotensin I1 subtype 2 (AT,) receptors appear early during renal embryonic development. Factors involved in the regulation of AT, receptors during renal development, however, have not been investigated. The present study was designed 1 ) to characterize the ontogeny of renal AT, gene expression during the last half of gestation in fetal sheep and newborn lambs, 2) to compare changes in AT, and AT, gene expression during renal development, 3) to determine the influence of A11 in modulating renal AT, and AT, gene expression during fetal life, and 4) to characterize the role of cortisol in modulating renal AT, gene expression during the last trimester of gestation in fetal sheep. To perform these studies, we first isolated and cloned a polymerase chain reaction product that has 92 and 90% homology with the cDNA encoding the human and rat AT, receptors, respectively. Using this sheep AT, cDNA probe, we demonstrated that the sheep AT, gene was encoded in a single locus. In addition, we showed that renal AT, mRNA expression was high early during fetal life (60-90-d gestation) and decreased rapidly thereafter. In contrast, the expression of renal AT, receptor gene was low at 60-d gestation and increased during the last trimester of gestation. We found that a continuous i.v. infusion (1 mL/h) of A11 (9.5 nM/h) for 24 h, which raised plasma A11 levels from 84 t-9 pg/mL to 210 i-21 pg/mL, decreased the expression of both renal AT, and AT, genes in third trimester fetal sheep. On the other hand, we observed that cortisol, known to decrease AT, gene expression in the fetus, had no effect on AT, gene expression. In summary, this study demonstrates that AII, but not glucocorticoids, contributes to the regulation of renal AT, gene expression during development and that there is differential regulation of AT, and AT, receptors. (2), and the expression of renin, angiotensinogen, and angiotensinconverting enzyme genes appear to be developmentally regulated (3-6).It has been suggested that A11 is implicated in the regulation of renal function (1) and renal growth (7) during development.The biologic effects of A11 are mediated by two distinct specific receptors (AT, and AT,) located in the plasma membrane of different tissues (8). Studies in rats (9, 10) and sheep (11) have shown that the expression of kidney AT, receptor mRNA is developmentally regulated. In the sheep, renal AT, mRNA expression is elevated during the last trimester of gestation and decreases during the second postnatal week (1 1).In the rat, the expression of renal AT, receptor mRNA is also higher in immature than in adult animals (12). Discrete expression of AT, receptor has been observed as early as 2 d of postnatal age in rat immature glomeruli (10).Both in situ hybridization and autoradiographic studies have also shown that AT, receptors are present in the fetal mesenchyme (13), in the mesonephros before its involution (14), in

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Section: Discussionsupporting

confidence: 66%

Differential Gene Expression and Regulation of Renal Angiotensin II Receptor Subtypes (AT1 and AT2) during Fetal Life in Sheep

et al. 1995

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“…We have also described the expression of AGTR1 and AGTR2 in trophoblast subpopulations at the maternal-fetal interface, with AGTR1 primarily expressed by the differentiated trophoblasts:syncytiotrophoblast and cell column extravillous trophoblasts, and AGTR2 by proliferating villous cytotrophoblasts. AGTR2 is abundantly expressed in murine, porcine and bovine placenta (Grady et al 1991, Nielsen et al 1996, Schauser et al 1998, and it is the predominant receptor present in human cycling endometrium and myometrium (Tsuzuki et al 1994, Ahmed et al 1995. However, previous reports in the literature of its expression in human placenta are conflicting (Cooper et al 1999, Anton et al 2008, Williams et al 2010.…”

Section: Discussionmentioning

confidence: 99%

Differential expression of angiotensin II type 1 and type 2 receptors at the maternal–fetal interface: potential roles in early placental development

Tower

Liu²,

Charlesworth

et al. 2010

Reproduction

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Angiotensin II (Ang II) is locally generated in the placenta and regulates syncytial transport, vascular contractility and trophoblast invasion. It acts through two receptor subtypes, AGTR1 and AGTR2 (AT1 and AT2), which typically mediate antagonising actions. The objectives of this study are to characterise the cellular distribution of AGTR1 and AGTR2 at the maternal-fetal interface and explore the effects on cytotrophoblast turnover. Low levels of AGTR2 mRNA were detected in first trimester placental homogenates using real-time PCR. Immunohistochemistry using polyclonal antibodies against AGTR1 and AGTR2 detected the receptors in first trimester placenta, decidua basalis and villous tip outgrowths in culture. Serial staining with cytokeratin-7 was used to identify extravillous trophoblasts (EVTs). AGTR1 was found in the syncytiotrophoblast microvillous membrane, in a subpopulation of villous cytotrophoblasts, and in Hofbauer cells. AGTR1 was strongly upregulated in cytotrophoblasts in cell columns and villous tip outgrowths, but was absent in interstitial and endovascular EVTs within the decidua. AGTR2 immunostaining was present in Hofbauer cells and villous cytotrophoblasts, but was absent from syncytiotrophoblast. Faint staining was detected in cell column cytotrophoblasts and villous outgrowths, but not in EVTs within the decidua. Both receptors were detected in placental homogenates by western blotting. Ang II significantly increased proliferation of cytotrophoblasts in both villous explants and villous tip outgrowths, but did not affect apoptosis. Blockade of AGTR1 and AGTR2 together abrogated this effect. This study shows specific expression patterns for AGTR1 and AGTR2 in distinct trophoblast populations at the maternal-fetal interface and suggests that Ang II plays a role in placental development and generation of EVTs.Reproduction (2010) 140 931-942

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“…of BR-A-657. 14) Nonspecific binding was estimated by adding 1 µm of Ang II to the incubation mixture. IC 50 values were determined by nonlinear least squares fitting of the inhibition curves with a sigmoid-Boltzmann equation regression analysis using GraphPad Prism 6.0.…”

Section: Methodsmentioning

confidence: 99%

Pharmacological Characterization of BR-A-657, a Highly Potent Nonpeptide Angiotensin II Receptor Antagonist

Lee

Kim

et al. 2013

Biological & Pharmaceutical Bulletin

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given orally at 1 and 3 mg/kg reduced blood pressure in conscious renal hypertensive rats. Taken together, these findings indicate that BR-A-657 is a potent and specific antagonist of Ang II at the AT 1 receptor subtype, and reveal the molecular basis responsible for the marked lowering of blood pressure in conscious rats.Key words BR-A-657; losartan; AT 1 receptor; angiotensin II pressor; renal hypertensive rat Hypertension is important not only because of its prevalence but also because it is a major modifiable risk factor of associated cardiovascular and renal complications. 1) Current guidelines emphasize the importance of managing hypertension to reduce substantial morbidity and mortality associated with cardiovascular events. 2-4)The renin angiotensin system (RAS) plays a pivotal role in cardiovascular regulation by blood pressure and fluid-electrolyte balance control. Angiotensin II (Ang II) circulates in the blood stream and is the principal mediator of the RAS system, stimulates vasoconstriction and the retention of salt and water, releases aldosterone from the adrenal glands, and modulates central effects such as drinking.5) The haemodynamic and cardiovascular effects of Ang II are all mediated by its binding to receptors on the surfaces of target cells within central and peripheral blood vessels, and within the heart and other organs.6) There are two distinct receptor subtypes, namely, AT 1 and AT 2 , and AT 1 receptors are thought to mediate the major effects of Ang II in cardiovascular, renal, neuronal, endocrine, hepatic, and other target cells. Many studies have shown that Ang II produces its biological activities by stimulating AT 1 receptors, especially in its blood pressure regulatory effect. Therefore, an Ang II receptor blocker (ARB) that blocks AT 1 receptors is considered to provide potential therapeutic strategies for the managements of hypertension and cardiovascular and renal diseases, and to date, several nonpeptide AT 1 receptor antagonists have been developed for the treatment of hypertension and heart failure. 7,8)

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Molecular Cloning and Expression of the Gene Encoding Human Angiotensin II Type 2 Receptor

Cited by 102 publications

References 0 publications

Differential Gene Expression and Regulation of Renal Angiotensin II Receptor Subtypes (AT1 and AT2) during Fetal Life in Sheep

Differential Gene Expression and Regulation of Renal Angiotensin II Receptor Subtypes (AT1 and AT2) during Fetal Life in Sheep

Differential expression of angiotensin II type 1 and type 2 receptors at the maternal–fetal interface: potential roles in early placental development

Pharmacological Characterization of BR-A-657, a Highly Potent Nonpeptide Angiotensin II Receptor Antagonist

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