Isolation of a cDNA encoding the vascular type-1 angiotensin II receptor

Murphy, Tamara C.; Alexander, R. Wayne; Griendling, Kathy K.; Runge, Marschall S.; Bernstein, Kenneth E.

doi:10.1038/351233a0

Cited by 1,185 publications

(530 citation statements)

References 22 publications

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“…In the literature there are competing theories about the underlying molecular mechanisms by which AT1 receptor expression may be upregulated in diabetic individuals, including transcriptional and post-transcriptional pathways. Among other stimuli, growth factors, progesterone, lipoproteins and insulin have been proposed to be involved in the regulation of AT1 receptor expression, and numerous consensus sequences were discovered within the promotor region of the AT1 receptor gene, including response elements for oestrogen, cyclic AMP or nuclear factor-κB [28]. However, the exact mechanisms of transcriptional control of AT1 receptor mRNA synthesis are still poorly understood.…”

Section: Discussionmentioning

confidence: 99%

The increased angiotensin II (type 1) receptor density in myocardium of type 2 diabetic patients is prevented by blockade of the renin–angiotensin system

et al. 2006

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Aims/hypothesis The angiotensin II (type 1) (AT1) receptor mediates many biological effects of the renin-angiotensin system (RAS), leading to remodelling of cardiac tissue. The present study was designed to analyse changes in the function and expression of the AT1 receptor as principal effector of the RAS in myocardium from type 2 diabetic patients compared with non-diabetic myocardium as control. In addition, we determined the effect of treatment with ACE inhibitors or AT1 receptor blockers on expression levels of the receptor in diabetic patients. Methods Gene expression of the AT1 receptor was analysed by quantitative RT-PCR and protein expression was determined by immunoblot analysis in human right atrial myocardium. We investigated functional coupling of the receptors by measuring contractility in isolated trabeculae stimulated with increasing concentrations of angiotensin II. Results Diabetic myocardium showed a significant increase in protein expression (170±16% of control) and median mRNA expression (186% of control) of the AT1 receptor.The additional receptors were functionally coupled, resulting in a stronger inotropic response upon stimulation with angiotensin II (89±5.5% vs 29±1.6% in controls), whereas receptor affinity was similar in both groups. However, myocardium from diabetic patients treated with ACE inhibitors or AT1 receptor blockers showed no increase in AT1 receptor expression. Conclusions/interpretation AT1 receptor expression in myocardium of type 2 diabetic patients is dynamic, depending on the level of glycaemic control and the activity of the RAS. These findings could at least in part explain the strong therapeutic benefit of RAS inhibition in diabetic patients.

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Section: Discussionmentioning

confidence: 99%

The increased angiotensin II (type 1) receptor density in myocardium of type 2 diabetic patients is prevented by blockade of the renin–angiotensin system

et al. 2006

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“…However, a new expression cloning technique resolved the problem of isolating AT1 receptor complementary DNA (cDNA) without purifying receptor proteins. In 1991, two groups adapted the expression cloning method, and successfully isolated full length cDNA of the AT1 receptor using the expression vectors pCDM8 and pCDNA1 [7], [8]. Messenger RNAs from cultured bovine adrenal zona glomerulosa cells or rat aortic vascular smooth muscle cells (VSMC) were used to prepare a cDNA library, which was inserted into pCDM8 or pCDNA1 respectively, divided into small pools, then expressed and selected in Cos7 cells.…”

Section: Cloning Of the At1 Receptormentioning

confidence: 99%

The angiotensin II type 1 receptor and receptor-associated proteins

et al. 2001

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The mechanisms of regulation, activation and signal transduction of the angiotensin II (Ang II) type 1 (AT1) receptor have been studied extensively in the decade after its cloning. The AT1 receptor is a major component of the renin-angiotensin system (RAS). It mediates the classical biological actions of Ang II. Among the structures required for regulation and activation of the receptor, its carboxyl-terminal region plays crucial roles in receptor internalization, desensitization and phosphorylation. The mechanisms involved in heterotrimeric G-protein coupling to the receptor, activation of the downstream signaling pathway by G proteins and the Ang II signal transduction pathways leading to specific cellular responses are discussed. In addition, recent work on the identification and characterization of novel proteins associated with carboxyl-terminus of the AT1 receptor is presented. These novel proteins will advance our understanding of how the receptor is internalized and recycled as they provide molecular mechanisms for the activation and regulation of G-protein-coupled receptors.

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“…Two kinds of Ang II receptors, AT1 and AT2, have been reported to exist in cardiac myocytes [15][16][17][18][19]. To examine which subtype of Ang II receptors is involved in the activation of p70 s6K, cardiac myocytes were preincubated with AT 1 receptor-specific antagonist, losartan (10 -5 M) or AT2 receptor-specific antagonist, PD123319 (10 -5 M) for 30 min and then stimulated with Ang II (10 -6 M) for 15 min.…”

Section: Ang H Stimulates P70 S6k Through At1 Receptormentioning

confidence: 99%

Activation of p70 S6 protein kinase is necessary for angiotensin II‐induced hypertrophy in neonatal rat cardiac myocytes

et al. 1996

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Although many lines of evidence have suggested that angiotensin II (Ang II) plays an important role in development of cardiac hypertrophy, the mechanism by which Ang II increases protein synthesis in cardiac myocytes remains unclear. It has been reported that the phosphorylation of $6 protein in 40 S ribosome is correlated to the efficiency of protein synthesis. In the present study, we have examined whether Ang II activates p70 $6 kinase (p70S6g), which has been reported to phosphorylate $6 protein.

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Isolation of a cDNA encoding the vascular type-1 angiotensin II receptor

Cited by 1,185 publications

References 22 publications

The increased angiotensin II (type 1) receptor density in myocardium of type 2 diabetic patients is prevented by blockade of the renin–angiotensin system

The increased angiotensin II (type 1) receptor density in myocardium of type 2 diabetic patients is prevented by blockade of the renin–angiotensin system

The angiotensin II type 1 receptor and receptor-associated proteins

Activation of p70 S6 protein kinase is necessary for angiotensin II‐induced hypertrophy in neonatal rat cardiac myocytes

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