Angiotensin AT4 Receptor

Chai, Siew Yeen; Mendelsohn, Frederick A.O.; Lee, Joohyung; Mustafa, Tomris; McDowall, Sharon G.; Albiston, Anthony L.

doi:10.1007/978-3-642-18495-6_22

Cited by 58 publications

(95 citation statements)

References 83 publications

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“…AT 1a and AT 1b exhibit similar ligand binding and signal transduction properties, and cannot be distinguished pharmacologically, but differ in their tissue distribution. 3 In addition to Ang II, shorter Ang metabolites, such as Ang IV 4,5 and Ang-(1-7), [6][7][8] demonstrate potent biological activity. The heptapeptide Ang-(1-7) is an Ang metabolite of special interest because it can often counteract the detrimental effects of Ang II, for example, its vasoconstrictive properties.…”

Section: Introductionmentioning

confidence: 99%

Hemodynamic effects of vasorelaxant compounds in mice lacking one, two or all three angiotensin II receptors

et al. 2012

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The renin-angiotensin system (RAS) has a vital role in regulating the cardiovascular system. The primary effector of the RAS is the octapeptide angiotensin (Ang) II, a potent regulator of blood pressure and water homeostasis. Ang II mediates its functions through the stimulation of two distinct receptors, AT 1 (two subtypes in rodents (AT 1a and AT 1b )) and AT 2 . It was shown that in addition to Ang II, shorter fragments of Ang are also biologically active. Ang-(1-7) came into focus because it opposes many of the detrimental effects of Ang II. However, it is still controversial whether Ang II receptors are involved in Ang-(1-7)-mediated signaling. To characterize the impacts of Ang II receptors on Ang-(1-7)-stimulated vascular relaxation, the effects of acute infusion of the three vasorelaxant compounds, that is, Ang-(1-7), bradykinin (BK) and acetylcholine (ACh), on heart rate (HR) and mean arterial pressure (MAP) were investigated in mice deficient for one, two or all three Ang II receptors. Ang-(1-7) and BK reduced MAP in wild-type, AT 1a /AT 1b -deficient and AT 2 -deficient mice. Although the change in absolute MAP values in the hypotensive triple knockouts (KO) could not be further reduced by both peptides, the percent change in MAP was comparable between the triple KO and wild-type mice. Both peptides did not alter the HR in all four genotypes. ACh significantly reduced absolute MAP values in all four genotypes with a similar percentage of reduction. In contrast to Ang-(1-7) and BK, ACh significantly reduced HR without genotypic differences. Our results generate proof that Ang-(1-7)-induced effects on MAP are mediated by a receptor that is independent of AT 1 and AT 2 .

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Section: Introductionmentioning

confidence: 99%

Hemodynamic effects of vasorelaxant compounds in mice lacking one, two or all three angiotensin II receptors

et al. 2012

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“…Protein purification and peptide sequencing showed that the AT4 receptor is an insulin-regulated aminopeptidase [54] . AT4 receptor is also found in the kidney, where this angiotensin-derived fragment can elicit many responses [55] . Aminopeptidases A and N are abundant in the kidney, especially in proximal nephron, and Ang Ⅳ is formed in the glomerulus [56,57] .…”

Section: New Members Of Ras: Ang Ii-derived Peptidesmentioning

confidence: 99%

“…Aminopeptidases A and N are abundant in the kidney, especially in proximal nephron, and Ang Ⅳ is formed in the glomerulus [56,57] . Ang Ⅳ increases blood flow in the kidney and decreases in Na + transport in proximal tubules [55] . Ang Ⅳ induces Ca 2+ mobilization in human proximal tubule cells [58] through the AT1 receptor.…”

Section: New Members Of Ras: Ang Ii-derived Peptidesmentioning

confidence: 99%

Renin-angiotensin system in the kidney: What is new?

Ferrão

Lara

Lowe

2014

WJN

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The renin-angiotensin system (RAS) has been known for more than a century as a cascade that regulates body fluid balance and blood pressure. Angiotensin Ⅱ (Ang Ⅱ) has many functions in different tissues; however it is on the kidney that this peptide exerts its main functions. New enzymes, alternative routes for Ang Ⅱ formation or even active Ang Ⅱ-derived peptides have now been described acting on Ang Ⅱ AT1 or AT2 receptors, or in receptors which have recently been cloned, such as Mas and AT4. Another interesting observation was that old members of the RAS, such as angiotensin converting enzyme (ACE), renin and prorenin, well known by its enzymatic activity, can also activate intracellular signaling pathways, acting as an outside-in signal transduction molecule or on the renin/(Pro)renin receptor. Moreover, the endocrine RAS, now is also known to have paracrine, autocrine and intracrine action on different tissues, expressing necessary components for local Ang Ⅱ formation. This in situ formation, especially in the kidney, increases Ang Ⅱ levels to regulate blood pressure and renal functions. These discoveries, such as the ACE2/Ang-(1-7)/Mas axis and its antangonistic effect rather than classical deleterious Ang Ⅱ effects, improves the development of new drugs for treating hypertension and cardiovascular diseases. Key words: Renin-angiotensin system; Angiotensin Ⅱ; Kidney; Hypertension treatment; Receptor Core tip: Activation of the angiotensin converting enzyme (ACE)/ Angiotensin Ⅱ (Ang Ⅱ)/AT1 axis leads to vasoconstriction, anti-diuresis, anti-natriuresis, release of aldosterone and anti-diuretic hormone, which can result in hypertension, renal and cardiovascular diseases. Inhibition of renin and ACE or blocking AT1 receptor is the most used therapies for heart failure and hypertension. Nevertheless, the discovery of local Ang Ⅱ synthesis, new Ang Ⅱ metabolites, receptors and axis of this system, makes possible the development of new drugs and strategies for renal and cardiovascular diseases treatment, such as activation of ACE2/Ang-(1-7)/ Mas axis, which presents opposite effects of AT1 activation by Ang Ⅱ.

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“…38 This field of research was redefined by the identification of the AT 4 -receptor as the transmembrane insulinregulated aminopeptidase (IRAP), with Ang IV and hemorphin ligands as competitive inhibitors but not substrates of IRAP. 39 Memory-potentiating AT 4 /IRAP ligands may act as follows: (i) potent inhibitors of IRAP favouring the action of endogenous promnestic peptides; (ii) modulators of glucose uptake interfering with GLUT4 traffick; (iii) agonists of IRAP as a receptor, in the sense of inducing signal transduction via its cytosolic domain. 39 Ang IV effects on memory could be related to elevated expression of ryanodine receptors and the subsequent increase in reticular calcium release.…”

Section: O P Y R I G H T J R a A S L I M I T E D R E P R O D U C T mentioning

confidence: 99%

“…39 Memory-potentiating AT 4 /IRAP ligands may act as follows: (i) potent inhibitors of IRAP favouring the action of endogenous promnestic peptides; (ii) modulators of glucose uptake interfering with GLUT4 traffick; (iii) agonists of IRAP as a receptor, in the sense of inducing signal transduction via its cytosolic domain. 39 Ang IV effects on memory could be related to elevated expression of ryanodine receptors and the subsequent increase in reticular calcium release. 40 The antiepileptogenic effects of Ang IV are partly mediated by an increase of adenosine A 1 -receptor density, 41 besides dopamine-related events: changes in extracellular dopamine levels in the striatum, prevention of D2-receptor decrease, and an area-specific increase in D1-receptors.…”

Section: O P Y R I G H T J R a A S L I M I T E D R E P R O D U C T mentioning

confidence: 99%

Review: Angiotensin Peptides and their Pleiotropic Actions

Haulică

Bild

Şerban

2005

J Renin Angiotensin Aldosterone Syst

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The concept of tissue renin-angiotensin systems (RAS) is now well established and it is now usual to think in terms of renal and tissue systems. At the same time it has emerged that angiotensin II (Ang II) is not the only biologically active peptide generated by the RAS. At least three others have been identified: the heptapeptide Ang III, the hexapeptide Ang IV and Ang 1-7. Specific receptors exits for the last two peptides. In addition, the range of possible physiological and pathophysiological properties for Ang II has been expanding. The current perception of the RAS is therefore that of a much more complex system than previously believed, with autocrine, paracrine and endocrine properties extending beyond the cardiovascular system. This mini-review focuses on the synthetic pathways of the Ang peptides and describes some of their pleiotropic actions. IntroductionOver the last three decades it has become increasingly clear that bioactive angiotensin peptides can be generated not only in the systemic circulation but also as local hormones in several tissues and organs. Classically, the renin-angiotensin system (RAS) has been considered a hormonal circulating system whose final and bioactive product angiotensin II (Ang II) is produced with participation of two critical enzymes, e.g. renin and the angiotensinconverting enzyme (ACE).

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Angiotensin AT4 Receptor

Cited by 58 publications

References 83 publications

Hemodynamic effects of vasorelaxant compounds in mice lacking one, two or all three angiotensin II receptors

Hemodynamic effects of vasorelaxant compounds in mice lacking one, two or all three angiotensin II receptors

Renin-angiotensin system in the kidney: What is new?

Review: Angiotensin Peptides and their Pleiotropic Actions

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