Non-canonical signalling and roles of the vasoactive peptides angiotensins and kinins

Costa-Neto, Cláudio M.; Duarte, Diego A.; Lima, Vanessa Batista de Sousa; Maria, Andréa Gutierrez; Prando, Érika C.; Rodríguez, Deisy Y.; Santos, Geisa A.; Souza, Pedro Paulo Chaves de; Parreiras-e-Silva, Lucas T.

doi:10.1042/cs20130414

Cited by 15 publications

(25 citation statements)

References 305 publications

(278 reference statements)

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“…Thus the conversion of Ang I to Ang II induced by ACE could be more important in the initiation and progression of healthy tissue to gingivitis and/or gingivitis to periodontitis rather than the maintenance of chronic periodontitis. Indeed, the classical actions of Ang II are usually attributed to the interaction with the AT 1 R, as reviewed elsewhere [ 34 ].…”

Section: Discussionmentioning

confidence: 99%

Functional Local Renin-Angiotensin System in Human and Rat Periodontal Tissue

et al. 2015

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The initiation or progression of periodontitis might involve a local renin-angiotensin system (RAS) in periodontal tissue. The aim of this study was to further characterize the local RAS in human and rat periodontal tissues between healthy and periodontally-affected tissue. Components of the RAS were investigated using in vitro, ex vivo and in vivo experiments involving both human and Wistar rat periodontium. Although not upregulated when challenged with P. gingivalis-lipopolysaccharide, human gingival and periodontal ligament fibroblasts expressed RAS components. Likewise, healthy and inflamed human gingiva expressed RAS components, some of which were shown to be functional, yet no differences in expression were found between healthy and diseased gingiva. However, in inflamed tissue the immunoreactivity was greater for the AT1R compared to AT2R in fibroblasts. When compared to healthy tissue, ACE activity was increased in human gingiva from volunteers with gingivitis. Human-gingiva homogenates generated Ang II, Ang 1-9 and Ang 1-7 when incubated with precursors. In gingiva homogenates, Ang II formation from Ang I was nearly abolished only when captopril and chymostatin were combined. Ang 1-7 formation was significantly greater when human gingiva homogenates were incubated with chymostatin alone compared to incubation without any inhibitor, only captopril, or captopril and chymostatin. In rat gingiva, RAS components were also found; their expression was not different between healthy and experimentally induced periodontitis (EP) groups. However, renin inhibition (aliskiren) and an AT1R antagonist (losartan) significantly blocked EP-alveolar-bone loss in rats. Collectively, these data are consistent with the hypothesis that a local RAS system is not only present but is also functional in both human and rat periodontal tissue. Furthermore, blocking AT1R and renin can significantly prevent periodontal bone loss induced by EP in rats.

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Section: Discussionmentioning

confidence: 99%

Functional Local Renin-Angiotensin System in Human and Rat Periodontal Tissue

et al. 2015

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“…Several reports have shown expression of kinin receptor in tumors and tumor cell lines 14 15 46 , and the use of antagonists, mainly for the B2 receptor, has been shown to decrease tumor growth and proliferation in many tumor types 12 13 , suggesting a pro-tumor role for the kinin B2 receptor. A less clear scenario is observed regarding the kinin B1 receptor.…”

Section: Discussionmentioning

confidence: 99%

“…Regarding tumor formation and progression, the role of KKS in this pathology is still poorly understood. The expression of kinin B1 and B2 receptors has been described in many tumor types, and several reports have shown a pro-tumor role of kinin B2 receptor 12 13 14 15 . For the kinin B1 receptor, a much less clear scenario appears.…”

mentioning

confidence: 99%

Host kinin B1 receptor plays a protective role against melanoma progression

Maria

Dillenburg-Pilla

Reis

et al. 2016

Sci Rep

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Melanoma is a very aggressive tumor that arises from melanocytes. Late stage and widely spread diseases do not respond to standard therapeutic approaches. The kallikrein-kinin system (KKS) participates in biological processes such as vasodilatation, pain and inflammatory response. However, the role of KKS in tumor formation and progression is not completely understood. The role of the host kinin B1 receptor in melanoma development was evaluated using a syngeneic melanoma model. Primary tumors and metastasis were respectively induced by injecting B16F10 melanoma cells, which are derived from C57BL/6 mice, subcutaneously or in the tail vein in wild type C57BL/6 and B1 receptor knockout mice (B1−/−). Tumors developed in B1−/− mice presented unfavorable prognostic factors such as increased incidence of ulceration, higher levels of IL-10, higher activation of proliferative pathways such as ERK1/2 and Akt, and increased mitotic index. Furthermore, in the metastasis model, B1−/− mice developed larger metastatic colonies in the lung and lower CD8+immune effector cells when compared with WT animals. Altogether, our results provide evidences that B1−/− animals developed primary tumors with multiple features associated with poor prognosis and unfavorable metastatic onset, indicating that the B1 receptor may contribute to improve the host response against melanoma progression.

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“…On the other hand, binding of AngII to the AT 1 receptor (AT1R) triggers Gq activation leading to phospholipase C (PLC) stimulation, production of inositol trisphosphate (IP 3 ) and diacylglycerol (DAG), intracellular calcium (Ca 2+ ) mobilization, activation of protein kinase C (PKC) and downstream cellular effectors. In addition, binding of AngII to AT1R has also been reported to activate Gi/o and G12/13 8 . AT1R activation accounts for most of the classical actions of AngII, including vasoconstriction, sodium and water reabsorption as well as cell growth, proliferation, and matrix deposition 9 .…”

Section: Introductionmentioning

confidence: 99%

Ang-(1-7) is an endogenous β-arrestin-biased agonist of the AT1 receptor with protective action in cardiac hypertrophy

Teixeira

Parreiras-e-Silva

Bruder‐Nascimento

et al. 2017

Sci Rep

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The renin-angiotensin system (RAS) plays a key role in the control of vasoconstriction as well as sodium and fluid retention mediated mainly by angiotensin (Ang) II acting at the AT1 receptor (AT1R). Ang-(1-7) is another RAS peptide, identified as the endogenous ligand of the Mas receptor and known to counterbalance many of the deleterious effects of AngII. AT1R signaling triggered by β-arrestin-biased agonists has been associated to cardioprotection. Because position 8 in AngII is important for G protein activation, we hypothesized that Ang-(1-7) could be an endogenous β-arrestin-biased agonist of the AT1R. Here we show that Ang-(1-7) binds to the AT1R without activating Gq, but triggering β-arrestins 1 and 2 recruitment and activation. Using an in vivo model of cardiac hypertrophy, we show that Ang-(1-7) significantly attenuates heart hypertrophy by reducing both heart weight and ventricular wall thickness and the increased end-diastolic pressure. Whereas neither the single blockade of AT1 or Mas receptors with their respective antagonists prevented the cardioprotective action of Ang1-7, combination of the two antagonists partially impaired the effect of Ang-(1-7). Taken together, these data indicate that Ang-(1-7) mediates at least part of its cardioprotective effects by acting as an endogenous β-arrestin-biased agonist at the AT1R.

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Non-canonical signalling and roles of the vasoactive peptides angiotensins and kinins

Cited by 15 publications

References 305 publications

Functional Local Renin-Angiotensin System in Human and Rat Periodontal Tissue

Functional Local Renin-Angiotensin System in Human and Rat Periodontal Tissue

Host kinin B1 receptor plays a protective role against melanoma progression

Ang-(1-7) is an endogenous β-arrestin-biased agonist of the AT1 receptor with protective action in cardiac hypertrophy

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