Significance of angiotensin 1–7 coupling with MAS1 receptor and other GPCRs to the renin‐angiotensin system: IUPHAR Review 22

The kidney is an important target of the renin‐ ANG ‐aldosterone system ( RAAS ). To date, several studies have demonstrated the existence of a local RAAS in various tissues, including the renal tissue. The mineralocorticoid aldosterone is known to play a critical role in the classical RAAS ; however, its effect on mesangial cells ( MC s) remains to be elucidated. Based on this, our aim was to investigate whether aldosterone stimulation can modulate the intracellular RAAS of immortalized human MC s by evaluating ANG ‐converting enzyme ( ACE )/ ANG II / ANG II receptor type 1 ( AT 1) and ANG ‐converting enzyme 2 ( ACE 2)/ ANG (1‐7)/ MAS receptor axes. To realise this, protein expression, enzyme activity, and immunofluorescence were performed under aldosterone stimulation and in the presence of the mineralocorticoid receptor ( MR ) antagonist spironolactone ( SPI ). We observed that high doses of aldosterone increase ACE activity. The effect of aldosterone on the catalytic activity of ACE was completely abolished with the pretreatment of SPI suggesting that the aldosterone‐induced cell injuries through ANG II release were attenuated. Aldosterone treatment also decreased the expression of MAS receptor, but did not alter the expression or the catalytic activity of ACE 2 and ANG (1‐7) levels. Spironolactone modulated the localization of ANG II and AT 1 receptor and decreased ANG (1‐7) and MAS receptor levels. Our data suggest that both aldosterone and the MR receptor antagonist can modulate both of these axes and that spironolactone can protect MC s from the damage induced by aldosterone.

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“…Indeed, several recent publications have highlighted the crosstalk that occurs between the MAS and ANG II receptors (Karnik et al. ).…”

Section: Discussionmentioning

confidence: 99%

Both aldosterone and spironolactone can modulate the intracellular ACE/ANG II/AT1 and ACE2/ANG (1‐7)/MAS receptor axes in human mesangial cells

et al. 2019

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“…A member of Mas-related GPCR family, MrgD, has been shown to react with ANG (1-7) to produce arachidonic acid (461). In addition, the MrgD receptor is responsive to Alamandine.…”

Section: Mrgdmentioning

confidence: 99%

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

Forrester

Booz

Sigmund

et al. 2018

Physiological Reviews

811

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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“…The renin-angiotensin system (RAS) plays a central role in the homeostatic control of the cardiovascular and renal systems, and in regulating the volume of extracellular fluid [206, 207]. The RAS consists of several enzymatic reactions that generate angiotensin II (ANG II).…”

Section: Mast Cells and The Renin-angiotensin Systemmentioning

confidence: 99%

“…Initially, renin cleaves angiotensinogen to produce ANG I, which is then hydrolyzed by the angiotensin-converting enzyme (ACE) to produce ANG II. This peptide acts on ANG II type 1 receptor (AT 1 R) and AT 2 R. ANG II promotes vasoconstriction, inflammation, salt and water reabsorption, and oxidative stress via the activation of AT 1 R [206, 207]. …”

Section: Mast Cells and The Renin-angiotensin Systemmentioning

confidence: 99%

Physiological Roles of Mast Cells: Collegium Internationale Allergologicum Update 2019

Varricchi

Rossi

Galdiero

et al. 2019

Int Arch Allergy Immunol

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Mast cells are immune cells which have a widespread distribution in nearly all tissues. These cells and their mediators are canonically viewed as primary effector cells in allergic disorders. However, in the last years, mast cells have gained recognition for their involvement in several physiological and pathological conditions. They are highly heterogeneous immune cells displaying a constellation of surface receptors and producing a wide spectrum of inflammatory and immunomodulatory mediators. These features enable the cells to act as sentinels in harmful situations as well as respond to metabolic and immune changes in their microenvironment. Moreover, they communicate with many immune and nonimmune cells implicated in several immunological responses. Although mast cells contribute to host responses in experimental infections, there is no satisfactory model to study how they contribute to infection outcome in humans. Mast cells modulate physiological and pathological angiogenesis and lymphangiogenesis, but their role in tumor initiation and development is still controversial. Cardiac mast cells store and release several mediators that can exert multiple effects in the homeostatic control of different cardiometabolic functions. Although mast cells and their mediators have been simplistically associated with detrimental roles in allergic disorders, there is increasing evidence that they can also have homeostatic or protective roles in several pathophysiological processes. These findings may reflect the functional heterogeneity of different subsets of mast cells.

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Significance of angiotensin 1–7 coupling with MAS1 receptor and other GPCRs to the renin‐angiotensin system: IUPHAR Review 22

Cited by 84 publications

References 216 publications

Both aldosterone and spironolactone can modulate the intracellular ACE/ANG II/AT1 and ACE2/ANG (1‐7)/MAS receptor axes in human mesangial cells

Both aldosterone and spironolactone can modulate the intracellular ACE/ANG II/AT1 and ACE2/ANG (1‐7)/MAS receptor axes in human mesangial cells

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

Physiological Roles of Mast Cells: Collegium Internationale Allergologicum Update 2019

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