International Union of Basic and Clinical Pharmacology. XCIX. Angiotensin Receptors: Interpreters of Pathophysiological Angiotensinergic Stimuli

Karnik, Sadashiva S.; Ünal, Hamiyet; Kemp, Jacqueline; Tirupula, Kalyan; Eguchi, Satoru; Vanderheyden, Patrick; Thomas, Walter G.

doi:10.1124/pr.114.010454

Cited by 255 publications

(317 citation statements)

References 1,066 publications

(1,131 reference statements)

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“…It is well accepted that most of the physiological and pathophysiological functions of ANG II are mediated through the AT1 receptor. In VSMCs, AT1 activation mediates vasoconstriction as well as hypertrophy, hyperplasia, and migration (257). Like AT1R, endothelin stimulation of G qcoupled ET-1 receptors or norepinephrine stimulation of G q -coupled ␣1-adrenoceptor also stimulates contraction and proliferation of VSMCs (208).…”

Section: Role Of Egfr In the Vasculaturementioning

confidence: 99%

Expression and Function of the Epidermal Growth Factor Receptor in Physiology and Disease

Chen

Zeng

Forrester

et al. 2016

Physiological Reviews

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191

156

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The epidermal growth factor receptor (EGFR) is the prototypical member of a family of membrane-associated intrinsic tyrosine kinase receptors, the ErbB family. EGFR is activated by multiple ligands, including EGF, transforming growth factor (TGF)-α, HB-EGF, betacellulin, amphiregulin, epiregulin, and epigen. EGFR is expressed in multiple organs and plays important roles in proliferation, survival, and differentiation in both development and normal physiology, as well as in pathophysiological conditions. In addition, EGFR transactivation underlies some important biologic consequences in response to many G protein-coupled receptor (GPCR) agonists. Aberrant EGFR activation is a significant factor in development and progression of multiple cancers, which has led to development of mechanism-based therapies with specific receptor antibodies and tyrosine kinase inhibitors. This review highlights the current knowledge about mechanisms and roles of EGFR in physiology and disease.

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Section: Role Of Egfr In the Vasculaturementioning

confidence: 99%

Expression and Function of the Epidermal Growth Factor Receptor in Physiology and Disease

Chen

Zeng

Forrester

et al. 2016

Physiological Reviews

Self Cite

191

156

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“…The system influences a large range of homeostatic and modulatory processes including regulation of salt and water balance, vasoconstriction, cell/tissue remodeling and dysfunction in the cardiovascular system. Angiotensin (AngII), the major bioactive peptide of the RAAS, mediates many of its effects by binding to two major G protein-coupled receptors (GPCRs): AngII type 1 receptor (AT1 receptor) and the AngII type 2 receptor (AT2 receptor) (1). Although the AT2 receptor is thought to oppose the effects of the AT1 receptor, many of the effects of AngII are mediated through the activation of the AT1 receptor.…”

Section: Introductionmentioning

confidence: 99%

“…The AT1 receptor is predominantly expressed in various tissues throughout the cardiovascular system including vascular smooth muscle, endothelium, heart and kidney. The AT1 receptor promotes intracellular signaling pathways through the activation of various protein kinases, subunits of nicotinamide adenine dinucleotide phosphate (NADPH) oxidase, growth factor receptor transactivation (1–5), or direct interactions with AT1 receptor interacting proteins such as Janus kinase 2 (JAK2), phospholipase C (PLC) γ1, AT1 receptor associated protein (ATRAP), type 1 angiotensin II receptor-associated protein (ARAP1) and Guanine nucleotide exchange factor (GEF)-like protein (GLP) (1, 2, 6, 7). …”

Section: Introductionmentioning

confidence: 99%

“…AT2 receptor stimulation causes vasorelaxation through protein kinase A (PKA)-dependent endothelial nitric oxide (NO) synthase (eNOS) activation or paracrine signaling induced by bradykinin/NO/cyclic GMP production (1, 8). Mice overexpressing the AT2 receptor exhibit vasodilation (11), and pharmacological stimulation of AT2 receptor promotes natriuresis, lowering of blood pressure, and inhibits AngII-mediated hypertension (12, 13).…”

Section: Introductionmentioning

confidence: 99%

“…However, Ang1-7 attenuates cardiac hypertrophy and fibrosis induced by AngII independent of alterations in blood pressure (22). While the Mas receptor is a GPCR, its G protein coupling is controversial and Mas may also signal G protein independently or constitutively without ligand binding (1). Please note that detailed review articles focused on Ang1-7/Mas functions and mechanisms have been published, whereas more emphasis is needed regarding Mas signaling and how it interacts with AT1 receptor signal transduction (19, 20).…”

Section: Introductionmentioning

confidence: 99%

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AT1 receptor signaling pathways in the cardiovascular system

Kawai

Forrester

O’Brien

et al. 2017

Pharmacological Research

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166

126

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The importance of the renin angiotensin aldosterone system in cardiovascular physiology and pathophysiology has been well described whereas the detailed molecular mechanisms remain elusive. The angiotensin II type 1 receptor (AT1 receptor) is one of the key players in the renin angiotensin aldosterone system. The AT1 receptor promotes various intracellular signaling pathways resulting in hypertension, endothelial dysfunction, vascular remodeling and end organ damage. Accumulating evidence shows the complex picture of AT1 receptor-mediated signaling; AT1 receptor-mediated heterotrimeric G protein-dependent signaling, transactivation of growth factor receptors, NADPH oxidase and ROS signaling, G protein-independent signaling, including the β-arrestin signals and interaction with several AT1 receptor interacting proteins. In addition, there is functional cross-talk between the AT1 receptor signaling pathway and other signaling pathways. In this review, we will summarize an up to date overview of essential AT1 receptor signaling events and their functional significances in the cardiovascular system.

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Angiotensin II type 2 receptor as a novel activator of brown adipose tissue in obesity

et al. 2023

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The angiotensin II type 2 receptor (AT2R) exerts vasorelaxant, anti‐inflammatory, and antioxidant properties. In obesity, its activation counterbalances the adverse cardiovascular effects of angiotensin II mediated by the AT1R. Preliminary results indicate that it also promotes brown adipocyte differentiation in vitro. Our hypothesis is that AT2R activation could increase BAT mass and activity in obesity. Five‐week‐old male C57BL/6J mice were fed a standard or a high‐fat (HF) diet for 6 weeks. Half of the animals were treated with compound 21 (C21), a selective AT2R agonist, (1 mg/kg/day) in the drinking water. Electron transport chain (ETC), oxidative phosphorylation, and UCP1 proteins were measured in the interscapular BAT (iBAT) and thoracic perivascular adipose tissue (tPVAT) as well as inflammatory and oxidative parameters. Differentiation and oxygen consumption rate (OCR) in the presence of C21 was tested in brown preadipocytes. In vitro, C21‐differentiated brown adipocytes showed an AT2R‐dependent increase of differentiation markers (Ucp1, Cidea, Pparg) and increased basal and H+ leak‐linked OCR. In vivo, HF‐C21 mice showed increased iBAT mass compared to HF animals. Both their iBAT and tPVAT showed higher protein levels of the ETC protein complexes and UCP1, together with a reduction of inflammatory and oxidative markers. The activation of the AT2R increases BAT mass, mitochondrial activity, and reduces markers of tissue inflammation and oxidative stress in obesity. Therefore, insulin reduction and better vascular responses are achieved. Thus, the activation of the protective arm of the renin–angiotensin system arises as a promising tool in the treatment of obesity.

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International Union of Basic and Clinical Pharmacology. XCIX. Angiotensin Receptors: Interpreters of Pathophysiological Angiotensinergic Stimuli

Cited by 255 publications

References 1,066 publications

Expression and Function of the Epidermal Growth Factor Receptor in Physiology and Disease

Expression and Function of the Epidermal Growth Factor Receptor in Physiology and Disease

AT1 receptor signaling pathways in the cardiovascular system

Angiotensin II type 2 receptor as a novel activator of brown adipose tissue in obesity

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