Attenuation of ligand-induced activation of angiotensin II type 1 receptor signaling by the type 2 receptor via protein kinase C

Inuzuka, Takayuki; Fujioka, Yoichiro; Tsuda, Masumi; Fujioka, Yoichiro; Satoh, Ayumi; Horiuchi, Kosui; Nishide, Shin‐ya; Nanbo, Asuka; Tanaka, Shinya; Ohba, Yusuke

doi:10.1038/srep21613

Cited by 41 publications

(38 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This notion is supported by our recent FRET studies in HEK cells expressing AT 2 R and MasR that their agonists alone do not affect FRET suggesting that these ligands do not promote or dissociate dimerization. 29 Along the same line of notion, other studies suggested that pretreatment of agonist or antagonist did not affect interactions of AT 2 R with AT 2 R, 36 AT 1 R 40 or B 2 R. 41 …”

Section: Discussionmentioning

confidence: 80%

Angiotensin II Type 2 Receptor and Receptor Mas Are Colocalized and Functionally Interdependent in Obese Zucker Rat Kidney

et al. 2017

View full text Add to dashboard Cite

The actions of angiotensin II type 2 receptor (AT2R) and the receptor Mas (MasR) are complex but show similar pro-natriuretic function; particularly AT2R expression and natriuretic function are enhanced in obese/diabetic rat kidney. In light of some reports suggesting a potential positive interaction between these receptors, we tested hypothesis that renal AT2R and MasR physically interact and are inter-dependent to stimulate cell signaling and promote natriuresis in obese rats. We found that infusion of AT2R agonist C21 in obese Zucker rats (OZR) increased urine flow (UF) and urinary Na-excretion (UNaV) which were attenuated by simultaneous infusion of the AT2R antagonist PD123319 or the MasR antagonist A-779. Similarly, infusion of MasR agonist Ang-(1-7) in OZR increased UF and UNaV, which were attenuated by simultaneous infusion of A-779 or PD123319. Experiment in isolated renal proximal tubules of OZR revealed that both the agonists C21 and Ang-(1-7) stimulated NO which was blocked by either of the receptor antagonists. Dual-labeling of AT2R and MasR in OZR kidney sections and human proximal tubule epithelial cells showed that AT2R and MasR are colocalized. The AT2R also co-immunoprecipitated with MasR in cortical homogenate of OZR. Immunoblotting of cortical homogenate cross-linked with zero length oxidative (sulfhydryl groups) cross-linker cupric-phenanthroline revealed a shift of AT2R and MasR bands upward with overlapping migration for their complexes which were sensitive to the reducing β-mercaptoethanol, suggesting involvement of –SH groups in cross linking. Collectively, the study reveals that AT2R and MasR are co-localized and functionally interdependent in terms of stimulating NO and promoting diuretic-natriuretic response.

show abstract

Section: Discussionmentioning

confidence: 80%

Angiotensin II Type 2 Receptor and Receptor Mas Are Colocalized and Functionally Interdependent in Obese Zucker Rat Kidney

et al. 2017

View full text Add to dashboard Cite

show abstract

“…5 The AT2R receptor stimulates various signaling pathways, which can be categorized into 3 broad types: regulation of protein phosphorylation, activation of phospholipases, and regulation of NO/cyclic guanosine monophosphate (cGMP). [25][26][27][28] Thus, the depressor phase may be due to the activation of PD123319-sensitive receptors and subsequent vasodilation, which can cause reduced peripheral resistance and even venous return.…”

Section: Discussionmentioning

confidence: 99%

Differences in Cardiovascular Responses to Alamandine in Two-Kidney, One Clip Hypertensive and Normotensive Rats

Javanmardi

Kouhpayeh

et al. 2017

Circ J

View full text Add to dashboard Cite

angiotensin II type 1 receptor (AT1R) blockers. These drugs block angiotensin II (Ang II) -the primary active peptide in the RAS, which has many effects on blood vessels, the heart, the brain and the kidneys -from activating AT1R. AT1R is one of the two well-characterized receptors that Ang II activates (in addition to angiotensin II type 2 receptor (AT2R)). 3 Losartan is an angiotensin receptor blocker, 4 which mainly antagonizes AT1R, while PD123319 can block AT2R and Mas-related G protein-coupled receptor D (MrgD) receptors. 5 Recently, numerous researchers have shown that the RAS has additional complex multifunctional peptides, enzymes and receptors. The discovery of the ACE2/angiotensin-(1-7) [Ang-(1-7)]/Mas receptor axis, 6,7 which counterbalances several functions of the ACE/Ang II/AT1R axis, has highlighted the complexity of the RAS. The ACE2/Ang-(1-7)/ Mas receptor axis acts as a counter-regulatory axis. 7 It involves the heptapeptide peptide known as Ang-(1-7), which acts through a G-protein-coupled receptor called Mas. 7 Ang-(1-7) can be hydrolyzed from Ang II by the action of peptidases such as ACE2 and prolyl endopepti-D espite major progress in the research on the pathogenesis and management of hypertension and other aspects of cardiometabolic disease, these conditions underlie a significant number cases of morbidity and mortality due to cardiovascular and chronic kidney disease. It is predicted that there will be an increase in the hypertension prevalence rate in the United States (US). Currently, this condition affects 29% of the population in this country; that is, ~65 million individuals. 1 The significance of the renin-angiotensin system (RAS) in the development of hypertension and cardiovascular disease is well known. 2 Chronic RAS activation is a significant causal factor associated with the gradual malfunction of organs such as blood vessels, the kidneys and the heart. 2 These consequences of RAS activation have encouraged the development of medicines that can deactivate the RAS and thereby prevent the associated pathologies. The first class of drugs aimed at RAS inhibition are known as angiotensin-converting enzyme (ACE1) inhibitors, and they came on the market in the late 1970 s. Background: Alamandine is a newly discovered component of the renin-angiotensin system, which regulates blood pressure. In this study, the effect of alamandine on cardiovascular parameters in two-kidney, one clip (2K1C) hypertensive rats and normotensive rats, and the possible roles of the angiotensin II type 1 receptor (AT1R) and the PD123319-sensitive receptors in mediating this effect was investigated.

show abstract

“…The mechanisms by which the heterodimers function are diverse. The AT 1 R-AT 2 R inhibitory interaction requires PKC-dependent AT 2 R phosphorylation (416). The AT 1 Rapelin receptor interaction inhibits AT 1 R ANG II binding (966).…”

Section: At 1 R-gpcr Heterodimermentioning

confidence: 99%

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

Forrester

Booz

Sigmund

et al. 2018

Physiological Reviews

821

780

View full text Add to dashboard Cite

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.

show abstract

Attenuation of ligand-induced activation of angiotensin II type 1 receptor signaling by the type 2 receptor via protein kinase C

Cited by 41 publications

References 35 publications

Angiotensin II Type 2 Receptor and Receptor Mas Are Colocalized and Functionally Interdependent in Obese Zucker Rat Kidney

Angiotensin II Type 2 Receptor and Receptor Mas Are Colocalized and Functionally Interdependent in Obese Zucker Rat Kidney

Differences in Cardiovascular Responses to Alamandine in Two-Kidney, One Clip Hypertensive and Normotensive Rats

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

Contact Info

Product

Resources

About