AT1 receptor signaling pathways in the cardiovascular system

Kawai, Tatsuo; Forrester, Steven J.; O’Brien, Shannon; Baggett, Ariele; Rizzo, Victor; Eguchi, Satoru

doi:10.1016/j.phrs.2017.05.008

Cited by 175 publications

(138 citation statements)

References 170 publications

(188 reference statements)

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“…AngII exerts physiological effects by combining with angiotensin II type 1 (AT1R) and type 2 (AT2R) receptors. AngII combines with AT1R to achieve most of its physiological effects [19,20]. AT1R is mainly located in kidney, liver, lungs, and vascular smooth muscle cells.…”

Section: A Brief Overview Of Rasmentioning

confidence: 99%

“…AT1R is mainly located in kidney, liver, lungs, and vascular smooth muscle cells. On binding to AngII, also mean to activate the classical arm (ACE/AngII/AT1R), AT1R stimulates vasoconstriction, sodium retention, sympathetic nervous activation, and reactive oxygen species (ROS) generation, coupled with deleterious effects, including endothelial dysfunction and induction of inflammatory, thrombotic, proliferative, and fibrotic processes [14,19,21]. Furthermore, researchers discovered that AngII regulates the homologous by binding to AT1R and this effect is related to cell types [22][23][24].…”

Section: A Brief Overview Of Rasmentioning

confidence: 99%

“…AT1R and AT2R are both components of classic RAS [19,21]. There are three possibilities for why ARB, which is closely related to AT1R and AT2R, can activate AMPK.…”

Section: At2r and Ampkmentioning

confidence: 99%

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AMPK: a balancer of the renin–angiotensin system

Liu

et al. 2019

Bioscience Reports

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The renin–angiotensin system (RAS) is undisputedly well-studied as one of the oldest and most critical regulators for arterial blood pressure, fluid volume, as well as renal function. In recent studies, RAS has also been implicated in the development of obesity, diabetes, hyperlipidemia, and other diseases, and also involved in the regulation of several signaling pathways such as proliferation, apoptosis and autophagy, and insulin resistance. AMP-activated protein kinase (AMPK), an essential cellular energy sensor, has also been discovered to be involved in these diseases and cellular pathways. This would imply a connection between the RAS and AMPK. Therefore, this review serves to draw attention to the cross-talk between RAS and AMPK, then summering the most recent literature which highlights AMPK as a point of balance between physiological and pathological functions of the RAS.

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Section: A Brief Overview Of Rasmentioning

confidence: 99%

Section: A Brief Overview Of Rasmentioning

confidence: 99%

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AMPK: a balancer of the renin–angiotensin system

Liu

et al. 2019

Bioscience Reports

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“…This finding became a critical foundation for the concept that ANG II acts like an inflammatory cytokine (99). The basic understanding that the AT 1 R contributes to hypertension and various complications via second messengers, activation of various ki-nases, and induction of remodeling and inflammation remains solid (470,1098).…”

Section: Introductionmentioning

confidence: 99%

Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology

Forrester

Booz

Sigmund

et al. 2018

Physiological Reviews

Self Cite

778

780

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The renin-angiotensin-aldosterone system plays crucial roles in cardiovascular physiology and pathophysiology. However, many of the signaling mechanisms have been unclear. The angiotensin II (ANG II) type 1 receptor (ATR) is believed to mediate most functions of ANG II in the system. ATR utilizes various signal transduction cascades causing hypertension, cardiovascular remodeling, and end organ damage. Moreover, functional cross-talk between ATR signaling pathways and other signaling pathways have been recognized. Accumulating evidence reveals the complexity of ANG II signal transduction in pathophysiology of the vasculature, heart, kidney, and brain, as well as several pathophysiological features, including inflammation, metabolic dysfunction, and aging. In this review, we provide a comprehensive update of the ANG II receptor signaling events and their functional significances for potential translation into therapeutic strategies. ATR remains central to the system in mediating physiological and pathophysiological functions of ANG II, and participation of specific signaling pathways becomes much clearer. There are still certain limitations and many controversies, and several noteworthy new concepts require further support. However, it is expected that rigorous translational research of the ANG II signaling pathways including those in large animals and humans will contribute to establishing effective new therapies against various diseases.

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“…Having established correct localization and the capacity to recruit β-arrestins for both the WT and the DRY mutants, we characterized functional activity of H1R DRY and AT1AR DRY mutants in a subset of signaling pathways. Both H1R and AT1AR can couple to Gq/11 and Gi proteins (H1R: reviewed in Seifert et al 2013, see also Violin et al 2003, Adjobo-Hermans et al 2011, van Unen et al 2016aAT1AR: reviewed in Hunyady &Catt 2006 andKawai et al 2017). The coupling of WT and DRY mutants to Gq proteins was evaluated using a FRET reporter for Gq activation AT1ARdry-p2A-mCh resulted in reproducible FRET signals, although they were much reduced in comparison to the responses mediated by the respective WT receptors: H1R DRY-and AT1AR DRY-mediated FRET signals reached, respectively, 12% and 17% of WT response.…”

Section: Gq Activation By Wt and Dry Mutants Of H1r And At1armentioning

confidence: 99%

Not so dry after all – DRY mutants of the AT1_A receptor and H1 receptor can induce G protein-dependent signaling

Pietraszewska-Bogiel

Joosen

Goedhart

2019

Preprint

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GPCRs are seven transmembrane spanning receptors that regulate a wide array of intracellular signaling cascades in response to various stimuli. To do so, they couple to different heterotrimeric G proteins and adaptor proteins, including arrestins.Importantly, arrestins were shown to regulate GPCR signaling through G proteins, as well as promote G protein-independent signaling events. Several research groups have reported successful isolation of exclusively G protein-dependent and arrestindependent signaling downstream of GPCR activation using biased agonists or receptor mutants incapable of coupling to either arrestins or G proteins. In the latter category, the DRY mutant of the angiotensin II type 1 receptor was extensively used to characterize functional selectivity downstream of AT1 A R. In an attempt to understand histamine 1 receptor signaling, we characterized the signaling capacity of the H1R DRY mutant in a panel of dynamic, live cell biosensor assays, including arrestin recruitment, heterotrimeric G-protein activation, Ca 2+ signaling, protein kinase C activity, GTP binding of RhoA, and activation of ERK1/2. Here we show that both H1R DRY mutant and the AT1 A R DRY mutant (used as a reference) are capable of efficient activation of G protein-mediated signaling. Therefore, contrary to common belief, they do not constitute suitable tools for dissection of arrestin-mediated, G proteinindependent signaling downstream of these receptors.

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AT1 receptor signaling pathways in the cardiovascular system

Cited by 175 publications

References 170 publications

AMPK: a balancer of the renin–angiotensin system

AMPK: a balancer of the renin–angiotensin system

Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology

Not so dry after all – DRY mutants of the AT1_A receptor and H1 receptor can induce G protein-dependent signaling

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AT1 receptor signaling pathways in the cardiovascular system

Cited by 175 publications

References 170 publications

AMPK: a balancer of the renin–angiotensin system

AMPK: a balancer of the renin–angiotensin system

Angiotensin II Signal Transduction: An Update on Mechanisms of Physiology and Pathophysiology

Not so dry after all – DRY mutants of the AT1A receptor and H1 receptor can induce G protein-dependent signaling

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Not so dry after all – DRY mutants of the AT1_A receptor and H1 receptor can induce G protein-dependent signaling