Angiotensin (1–7) does not interact directly with MAS1, but can potently antagonize signaling from the AT1 receptor

Gaidarov, Ibragim; Adams, John W.; Frazer, John; Anthony, Todd L.; Chen, Xiaohua; Gatlin, Joel; Semple, Graeme; Unett, David J.

doi:10.1016/j.cellsig.2018.06.007

Cited by 48 publications

(53 citation statements)

References 75 publications

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“…Moreover, AT 1 R can form heterodimers with the Mas receptor, which inhibits the activity of AT 1 R 12 . Using radiolabelling and dynamic mass redistribution experi ments in cells overexpressing the Mas receptor, Gaidarov and colleagues found that although angiotensin 1-7 can antagonize angiotensin II signalling, angiotensin 1-7 does not bind directly to the Mas receptor 13 . These data conflict with an earlier study that demonstrated binding of fluorescent or 125 I labelled angiotensin 1-7 to the Mas receptor 14 .…”

Section: Receptorsmentioning

confidence: 99%

“…These data conflict with an earlier study that demonstrated binding of fluorescent or 125 I labelled angiotensin 1-7 to the Mas receptor 14 . Gaidarov and colleagues noted that in the absence of the Mas receptor, angiotensin 1-7 has no effect on angiotensin II signalling 13 . However, the investigators also reiterated that rigorously controlled experiments demonstrating interactions between angiotensin 1-7 and the Mas receptor are very scarce.…”

Section: Receptorsmentioning

confidence: 99%

“…However, the investigators also reiterated that rigorously controlled experiments demonstrating interactions between angiotensin 1-7 and the Mas receptor are very scarce. Moreover, given that their findings suggest that angiotensin 1-7 does not bind to the Mas receptor, the researchers hypothe sized that any cardioprotective effects of angiotensin 1-7 might be attributable to antagonism of angio tensin II signalling 13 . Nevertheless, additional studies are required to confirm whether angiotensin 1-7 is an endogenous agonist of the Mas receptor.…”

Section: Receptorsmentioning

confidence: 99%

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Counter-regulatory renin–angiotensin system in cardiovascular disease

et al. 2019

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| The renin-angiotensin system is an important component of the cardiovascular system. Mounting evidence suggests that the metabolic products of angiotensin I and IIinitially thought to be biologically inactive -have key roles in cardiovascular physiology and pathophysiology. This non-canonical axis of the renin-angiotensin system consists of angiotensin 1-7 , angiotensin 1-9, angiotensin-converting enzyme 2, the type 2 angiotensin II receptor (AT 2 R), the proto-oncogene Mas receptor and the Mas-related G protein-coupled receptor member D. Each of these components has been shown to counteract the effects of the classical reninangiotensin system. This counter-regulatory renin-angiotensin system has a central role in the pathogenesis and development of various cardiovascular diseases and, therefore, represents a potential therapeutic target. In this Review , we provide the latest insights into the complexity and interplay of the components of the non-canonical renin-angiotensin system, and discuss the function and therapeutic potential of targeting this system to treat cardiovascular disease.

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Section: Receptorsmentioning

confidence: 99%

Section: Receptorsmentioning

confidence: 99%

Section: Receptorsmentioning

confidence: 99%

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Counter-regulatory renin–angiotensin system in cardiovascular disease

et al. 2019

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“…Ang II showed picomolar potency in an inositol phosphate accumulation assay, and the peptide caused a biphasic concentration‐dependent increase in Erk1/2 phosphorylation with EC 50 values in the picomolar and nanomolar range (Gaidarov et al, ). Addition of the AT 1 receptor antagonist, losartan, almost completely inhibited both the picomolar and nanomolar Ang II responses, suggesting that Ang II acts primarily via the AT 1 receptor (Gaidarov et al, ). Interestingly, ultra‐potent responses to Ang II could also be observed using a dynamic mass redistribution (DMR) assay.…”

Section: Ultra‐sensitive Gpcr Signalling: Evidence For Angiotensin Rementioning

confidence: 99%

“…Stimulation of cells with 10 pM Ang II caused a slow change in DMR, which reached a plateau at 20 min and was sustained for at least 80 min following drug addition (Gaidarov et al, ). In contrast, stimulation of the same cells with 100 nM Ang II caused a very transient increase in DMR which peaked at 5 min, then dropped to a negative peak at 30 min before a slow increase in DMR to baseline levels by 80 min (Gaidarov et al, ). Therefore, ultra‐low versus high concentrations of Ang II generated distinct temporal profiles of receptor activation.…”

Section: Ultra‐sensitive Gpcr Signalling: Evidence For Angiotensin Rementioning

confidence: 99%

Signalling in response to sub‐picomolar concentrations of active compounds: Pushing the boundaries of GPCR sensitivity

Civciristov

Halls

2019

British J Pharmacology

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There is evidence for ultra‐sensitive responses to active compounds at concentrations below picomolar levels by proteins and receptors found in species ranging from bacteria to mammals. We have recently shown that such ultra‐sensitivity is also demonstrated by a wide range of prototypical GPCRs, and we have determined the molecular mechanisms behind these responses for three family A GPCRs: the relaxin receptor, RXFP1; the β2‐adrenoceptor; and the M3 muscarinic ACh receptor. Interestingly, there are reports of similar ultra‐sensitivity by more than 15 human GPCR families, in addition to other human receptors and channels. These occur through a diverse range of signalling pathways and produce modulation of important physiological processes, including neuronal transmission, chemotaxis, gene transcription, protein/ion uptake and secretion, muscle contraction and relaxation, and phagocytosis. Here, we summarise the accumulating evidence of ultra‐sensitive receptor signalling to show that this is a common, though currently underappreciated, property of GPCRs. Linked Articles This article is part of a themed section on Adrenoceptors—New Roles for Old Players. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.14/issuetoc

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Small Activating RNA Modulation of the G Protein‐Coupled Receptor for Cancer Treatment

et al. 2022

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G protein-coupled receptors (GPCRs) are the most common and important drug targets. However, >70% of GPCRs are undruggable or difficult to target using conventional chemical agonists/antagonists. Small nucleic acid molecules, which can sequence-specifically modulate any gene, offer a unique opportunity to effectively expand drug targets, especially those that are undruggable or difficult to address, such as GPCRs. Here, the authors report for the first time that small activating RNAs (saRNAs) effectively modulate a GPCR for cancer treatment. Specifically, saRNAs promoting the expression of Mas receptor (MAS1), a GPCR that counteracts the classical angiotensin II pathway in cancer cell proliferation and migration, are identified. These saRNAs, delivered by an amphiphilic dendrimer vector, enhance MAS1 expression, counteracting the angiotensin II/angiotensin II Receptor Type 1 axis, and leading to significant suppression of tumorigenesis and the inhibition of tumor progression of multiple cancers in tumor-xenografted mouse models and patient-derived tumor models. This study provides not only a new strategy for cancer therapy by targeting the renin-angiotensin system, but also a new avenue to modulate GPCR signaling by RNA activation.

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Angiotensin (1–7) does not interact directly with MAS1, but can potently antagonize signaling from the AT1 receptor

Cited by 48 publications

References 75 publications

Counter-regulatory renin–angiotensin system in cardiovascular disease

Counter-regulatory renin–angiotensin system in cardiovascular disease

Signalling in response to sub‐picomolar concentrations of active compounds: Pushing the boundaries of GPCR sensitivity

Small Activating RNA Modulation of the G Protein‐Coupled Receptor for Cancer Treatment

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