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Angiotensin receptors
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	AT1
	AT2

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AT₂

Previous and Unofficial Names AII-2 AII β AII-A Structural Information class A G protein-coupled receptor Species TM AA Chromosomal Location Gene Name Reference Human 7 363 Xq22-q23 AGTR2 2,56 Rat 7 363 Xq34 Agtr2 2 Mouse 7 363 X12.5cM Agtr2 57

Contents: Previous and Unofficial Names Structural Information Database Links Agonists Antagonists Transduction Mechanisms Tissue Distribution Functional Assays Physiological Functions Physiological Consequences of Altering Gene Expression Biologically Significant Variants Receptor Comments

Database Links
ChEMBL Target	10692 (Hs), 10026 (Rn)
Ensembl	ENSG00000180772 (Hs), ENSMUSG00000068122 (Mm)
Entrez Gene	186 (Hs), 11609 (Mm), 24182 (Rn)
GeneCards	AGTR2 (Hs)
HomoloGene	20172 (Hs)
OMIM	300034 (Hs)
PharmGKB Gene	PA44 (Hs)
Protein Ontology (PRO)	PRO:000001191 (Hs)
RefSeq Nucleotide	NM_000686 (Hs), NM_007429 (Mm), NM_012494 (Rn)
RefSeq Protein	NP_000677 (Hs), NP_031455 (Mm), NP_036626 (Rn)
UniGene Hs.	405348 (Hs)
UniProt	P50052 (Hs), P35374 (Mm), P35351 (Rn)
Wikipedia	AT2

Search for 3D structures on the PDB
Search using keywords: Angiotensin receptors AT2	Search using accession numbers: P35351 || P50052 || P35374

Agonists
Key to terms and symbols	View all chemical structures	Click column headers to sort
Ligand Sp. Action Affinity Units Reference CGP42112 Hs Partial agonist 10.6 pKd 49,121-122 ang III Hs Full agonist 10.4 pKd 28,49,121 angiotensin II Hs Full agonist 10.2 pKd 49,121,124 [p-aminoPhe6] ang II Rn Full agonist 9.1 – 9.4 pKd 49,123 ang I Hs Full agonist 7.3 pIC50 121
View species-specific agonist tables
Agonist Comments
The natural ligands Ang I, Ang II, Ang III do not distinguish between the AT1 and AT2 receptors. CGP42112 behaves like an AT1 antagonist at high concentration (Ki 1.7 µM) [28,58]. The binding of tissue expressing exclusively the AT2 receptor is not affected by GTP or its analogues [59]. In contrast, an AT2 receptor sensitive to GTPgS and pertussis toxin has been identified in rat brain [60].

Antagonists
Key to terms and symbols	View all chemical structures	Click column headers to sort
Ligand Sp. Action Affinity Units Reference PD123319 Hs Antagonist 8.7 – 9.2 pKd 49,104,126 PD123177 Rn Antagonist 8.5 – 9.5 pIC50 61,103,125 saralasin Rn Antagonist 9.0 pIC50 61
View species-specific antagonist tables
Antagonist Comments
Saralasin is a non specific antagonist, which does not distinguish the AT1 and AT2 receptors [61].

Primary Transduction Mechanisms
Transducer	Effector/Response
Gi/Go family	Phospholipase A2 stimulation Other - See Comments
Comments:  The AT2 receptor appear to bind to Gia2 or Gia3 [68]. Depending on the tissues, activation of the AT2 receptor 1) stimulates Tyr and Ser/Thr phosphatases (MKP-1, PP2A, SHP-1) and protein dephosphorylation, 2) regulates the nitric-oxide-cGMP system and 3) stimulates phospholipase A2, release arachidonic acid and activates the Na+/HCO3 symporter [7,69-70]
References:  68,71-72

Secondary Transduction Mechanisms
Transducer	Effector/Response
Gi/Go family	Other - See Comments
Comments:  Activation of the AT2 receptor leads to MAP kinase inactivation, opening of delayed-rectifier K channel and closing of T-type Ca channels [73-74] N.B.: The AT2 receptor does not require receptor phosphorylation or heterotrimeric Gαβγ protein to be active [75].
References:

Tissue Distribution
Non pregnant uterus, heart, lung, kidney. Species:  Human Technique:  immunocytochemistry. References:  7
The expression is developmentally regulated: foetus >> adult; adrenal medulla > inferior olive, brain >>heart, kidney, ovary, myometrium, endothelial cells, adventitia, pancreas. Liver and pituitary appear devoid of AT2 receptors. Species:  Rat Technique:  Northern blotting. References:  7,104-105

Functional Assays
Nitric Oxyde formation and increased cGMP Species:  Rat Tissue:  kidney, heart Response measured:  cGMP References:  98-100
No functional assays really well established. Inhibition of cell growth leading to apoptosis Species:  Rat Tissue:  Confluent and quiescent neonatal cardiomyocyte, R3T3 fibroblast or PC12W pheochromocytoma cell lines Response measured:  Radiolabelled thymidine incorporation, DNA fragmentation, Bcl2/Bax; References:  101-103

Physiological Functions
Inhibition of cell growth and stimulation of apoptosis in vitro and in vivo Species:  Human Tissue:  PC12W, VSMC, endothelial cells, cardiomyocytes, R3T3 fibroblast, heart, kidney References:  7,62,65-67,101,106-112
Vasodilation (still controversial) Species:  Rat Tissue:  Vessel References:  7,62,65-66,113
Vascular hypertrophy and fibrosis (controversial) Species:  Rat Tissue:  Not specified References:  7,62,65-66
Neuronal cell differentiation and nerve regeneration Species:  Rat Tissue:  NG108-15, PC12W References:  7,114-115
Diuresis and natriuresis (controversial) Species:  Mouse Tissue:  AT2 KO mice References:  81
Increased cGMP and NO Species:  Human Tissue:  Kidney, coronary artery, aorta, heart, neurite References:  7,62,65-66,76-77,98-100,113,116-120

Physiological Consequences of Altering Gene Expression
AGTR2 deletion No gross anatomical defect or deformity; increased sensitivity to Ang II probably linked to an increased AT1 receptor expression, delay in vascular smooth muscle differentiation, attenuation of exploratory behavior, stimulation of dipsogenesis, reduced fibrosis and collagen expression, increased or reduced cardiac and vascular remodeling, anti-diuresis and anti-natriuresis, increased anti-inflammatory and pro-atherosclerotic mediators. Species:  Mouse Tissue:  Technique:  Gene targeting in embryonic stem cells. References:  76-80
AGTR2 overexpression No effect on cardiac hypertrophy or attenuation of cardiac remodeling and of perivascular fibrosis, stimulation of collagen synthesis in SMC and mesangial cells but inhibition in fibroblasts, increased bradykinin and nitric oxide formation. Over expression of the AT2 receptor down-regulated the AT1 receptor. Species:  Rat Tissue:  Technique:  Transgenesis. References:  78,81-94

Biologically Significant Variants
AGTR2, Gly21Val, Arg324Gln, Ile337Val,1-BPDEL, 395T have been associated with mental retardation Type:  Single nucleotide polymorphism. Species:  Human References:  95
AGTR2, Ala1332Gly MIM300034. Association with congenital anomalies of the kidney and urinary tract. This however was not confirmed in the pathogenesis of primary familial vesicoureteral reflux Ala1675G was associated with coronary risk especially in hypertensive patients. The G allele cerriers appears protected. Type:  Single nucleotide polymorphism. Species:  Human References:  23,96-97

Receptor Comments
The ATGR2 appears to be re-expressed or up-regulated after vascular injury, myocardial infarction, cardiac failure or wound healing, possibly reflecting re-activation of a foetal genetic programme [7,62-64] Preclinical in vitro and in vivo studies indicated that the AT2 receptor counterbalances the effect of the AT1 receptor [7,62,65-67]

To cite this receptor data page, please use the following:

Wayne Alexander, Kenneth E. Bernstein, Kevin J. Catt, Marc de Gasparo, Theodore L. Goodfriend, Mastgugu Horiuchi, Ahsan Husain, Tadashi Inagami, Pieter B. M. W. M. Timmermans, Thomas Unger.
Angiotensin receptors: AT₂. Last modified on 2010-06-28. Accessed on 2010-09-03. IUPHAR database (IUPHAR-DB), http://www.iuphar-db.org/DATABASE/ObjectDisplayForward?objectId=35.

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