Angiotensin II receptor type 1

Angiotensin II receptor type 1 (AT1) is a G_q/11-coupled G protein-coupled receptor (GPCR) and the best characterized angiotensin receptor. It is encoded in humans by the AGTR1 gene. AT1 has vasopressor effects and regulates aldosterone secretion. It is an important effector controlling blood pressure and volume in the cardiovascular system. Angiotensin II receptor blockers are drugs indicated for hypertension, diabetic nephropathy and congestive heart failure.

AGTR1
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4YAY, 4ZUD
Identifiers
Aliases	AGTR1, AG2S, AGTR1B, AT1, AT1AR, AT1B, AT1BR, AT1R, AT2R1, HAT1R, angiotensin II receptor type 1
External IDs	OMIM: 106165; MGI: 87964; HomoloGene: 3556; GeneCards: AGTR1; OMA:AGTR1 - orthologs
Gene location (Human) Chr. Chromosome 3 (human) Band 3q24 Start 148,697,784 bp End 148,743,008 bp
Gene location (Mouse) Chr. Chromosome 13 (mouse) Band 13 A3.2|13 13.19 cM Start 30,520,424 bp End 30,566,850 bp
RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in skin of hip placenta subcutaneous adipose tissue liver right lobe of liver right adrenal gland left adrenal gland adrenal cortex left adrenal cortex right adrenal cortex Top expressed in adrenal gland interventricular septum left lobe of liver lumbar spinal ganglion prostate myocardium of ventricle human kidney lobe of prostate right kidney sciatic nerve More reference expression data BioGPS More reference expression data
Gene ontology Molecular function G protein-coupled receptor activity angiotensin type II receptor activity angiotensin type I receptor activity signal transducer activity bradykinin receptor binding protein binding protein heterodimerization activity Cellular component integral component of membrane membrane plasma membrane integral component of plasma membrane intracellular anatomical structure Biological process positive regulation of protein metabolic process positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway positive regulation of inflammatory response maintenance of blood vessel diameter homeostasis by renin-angiotensin positive regulation of phospholipase A2 activity regulation of renal sodium excretion kidney development positive regulation of cholesterol esterification phospholipase C-activating angiotensin-activated signaling pathway positive regulation of cytosolic calcium ion concentration angiotensin-activated signaling pathway renin-angiotensin regulation of aldosterone production phospholipase C-activating G protein-coupled receptor signaling pathway positive regulation of macrophage derived foam cell differentiation positive regulation of reactive oxygen species metabolic process regulation of vasoconstriction low-density lipoprotein particle remodeling regulation of cell population proliferation regulation of cell growth Rho protein signal transduction positive regulation of NAD(P)H oxidase activity regulation of inflammatory response cell chemotaxis regulation of systemic arterial blood pressure by renin-angiotensin calcium-mediated signaling signal transduction blood vessel diameter maintenance G protein-coupled receptor signaling pathway positive regulation of blood vessel endothelial cell proliferation involved in sprouting angiogenesis inflammatory response Sources:Amigo / QuickGO
Orthologs Species Human Mouse Entrez 185 11607 Ensembl ENSG00000144891 ENSMUSG00000049115 UniProt P30556 P29754 RefSeq (mRNA) NM_032049 NM_000685 NM_004835 NM_009585 NM_031850 NM_001382736 NM_001382737 NM_177322 RefSeq (protein) NP_000676 NP_004826 NP_033611 NP_114038 NP_114438 NP_001369665 NP_001369666 NP_796296 Location (UCSC) Chr 3: 148.7 – 148.74 Mb Chr 13: 30.52 – 30.57 Mb PubMed search
Wikidata
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Signaling cascade

The angiotensin receptor is activated by the vasoconstricting peptide angiotensin II. The activated receptor in turn couples to G_q/11 and thus activates phospholipase C and increases the cytosolic Ca²⁺ concentrations, which in turn triggers cellular responses such as stimulation of protein kinase C. Activated receptor also inhibits adenylate cyclase in hepatocytes and activates various tyrosine kinases.

Function

The AT1 receptor mediates the major cardiovascular effects of angiotensin II. Effects include vasoconstriction, aldosterone synthesis and secretion, increased vasopressin secretion, cardiac hypertrophy, augmentation of peripheral noradrenergic activity, vascular smooth muscle cells proliferation, decreased renal blood flow, renal renin inhibition, renal tubular sodium reuptake, modulation of central sympathetic nervous system activity, cardiac contractility, central osmocontrol and extracellular matrix formation. The main function of angiotensin II in the brain is to stimulate drinking behavior, an effect that is mediated by the AT1 receptor.

Clinical significance

Due to the hemodynamic pressure and volume effects mediated by AT1 receptors, AT1 receptor antagonists are widely prescribed drugs in the management of hypertension and stable heart failure.

Animal studies

Elements of the renin-angiotensin system have been widely studied in a large variety of vertebrate animals including amphibians, reptiles, birds, and mammals.

AT1 receptor blockers have been shown to reduce fear memory recall in mice, but the reliability and relevance of this finding are to be determined.

Gene

It was previously thought that a related gene, denoted as AGTR1B, existed; however, it is now believed that there is only one type 1 receptor gene in humans. At least four transcript variants have been described for this gene. Additional variants have been described but their full-length nature has not been determined. The entire coding sequence is contained in the terminal exon and is present in all transcript variants.

A huge number of polymorphisms is reported in the databases for AT1R which provide an avenue to explore these polymorphisms for their implications in protein structure, function and drug efficacy. Methods In the current study all the SNPs (10234) reported in NCBI were analyzed and SNPs which were important in protein structure and drug interactions were identified. Structures of these polymorphic forms were modeled and in silico drug interaction studies were carried out. Results Result of the interaction studies with polymorphism was in correlation with the reported case. Two SNP mutated structures of AT1R i.e. rs780860717 (G288T), rs868647200 (A182C) shows considerably less binding affinities in case of all angiotensin receptor blockers (ARBs).

Interactions

Angiotensin II receptor type 1 has been shown to interact with Zinc finger and BTB domain-containing protein 16. The protein's mRNA has been reported to interact with Mir-132 microRNA as part of an RNA silencing mechanism that reduces receptor expression.

References

• This article incorporates text from the United States National Library of Medicine, which is in the public domain.

Further reading

• Matsusaka T, Ichikawa I (1997). "Biological functions of angiotensin and its receptors". Annual Review of Physiology. 59: 395–412. doi:10.1146/annurev.physiol.59.1.395. PMID 9074770.
• Allen AM, Moeller I, Jenkins TA, Zhuo J, Aldred GP, Chai SY, Mendelsohn FA (September 1998). "Angiotensin receptors in the nervous system". Brain Research Bulletin. 47 (1): 17–28. doi:10.1016/S0361-9230(98)00039-2. PMID 9766385. S2CID 24936475.
• Berry C, Touyz R, Dominiczak AF, Webb RC, Johns DG (December 2001). "Angiotensin receptors: signaling, vascular pathophysiology, and interactions with ceramide". American Journal of Physiology. Heart and Circulatory Physiology. 281 (6): H2337–H2365. doi:10.1152/ajpheart.2001.281.6.H2337. PMID 11709400. S2CID 41296327.
• Arima S, Ito S (November 2001). "New insights into actions of the renin-angiotensin system in the kidney: concentrating on the Ang II receptors and the newly described Ang-(1-7) and its receptor". Seminars in Nephrology. 21 (6): 535–543. doi:10.1053/snep.2001.26792. PMID 11709801.
• Stowasser M, Gunasekera TG, Gordon RD (December 2001). "Familial varieties of primary aldosteronism". Clinical and Experimental Pharmacology & Physiology. 28 (12): 1087–1090. doi:10.1046/j.1440-1681.2001.03574.x. PMID 11903322. S2CID 23091842.
• Padmanabhan N, Padmanabhan S, Connell JM (December 2000). "Genetic basis of cardiovascular disease--the renin-angiotensin-aldosterone system as a paradigm". Journal of the Renin-Angiotensin-Aldosterone System. 1 (4): 316–324. doi:10.3317/jraas.2000.060. PMID 11967817.
• Thibonnier M, Coles P, Thibonnier A, Shoham M (2002). "Chapter 14 Molecular pharmacology and modeling of vasopressin receptors". Vasopressin and Oxytocin: From Genes to Clinical Applications. Progress in Brain Research. Vol. 139. pp. 179–96. doi:10.1016/S0079-6123(02)39016-2. ISBN 978-0-444-50982-6. PMID 12436935.
• Elton TS, Martin MM (March 2003). "Alternative splicing: a novel mechanism to fine-tune the expression and function of the human AT1 receptor". Trends in Endocrinology and Metabolism. 14 (2): 66–71. doi:10.1016/S1043-2760(02)00038-3. PMID 12591176. S2CID 45146964.
• Saavedra JM, Benicky J, Zhou J (2007). "Mechanisms of the Anti-Ischemic Effect of Angiotensin II AT( 1 ) Receptor Antagonists in the Brain". Cellular and Molecular Neurobiology. 26 (7–8): 1099–1111. doi:10.1007/s10571-006-9009-0. PMID 16636899. S2CID 20245643.
• Oliveira L, Costa-Neto CM, Nakaie CR, Schreier S, Shimuta SI, Paiva AC (April 2007). "The angiotensin II AT1 receptor structure-activity correlations in the light of rhodopsin structure". Physiological Reviews. 87 (2): 565–592. doi:10.1152/physrev.00040.2005. PMID 17429042.
• Ariza AC, Bobadilla NA, Halhali A (2007). "[Endothelin 1 and angiotensin II in preeeclampsia]". Revista de Investigacion Clinica. 59 (1): 48–56. PMID 17569300.
• Xia Y, Zhou CC, Ramin SM, Kellems RE (September 2007). "Angiotensin receptors, autoimmunity, and preeclampsia". Journal of Immunology. 179 (6): 3391–3395. doi:10.4049/jimmunol.179.6.3391. PMC 3262172. PMID 17785770.
• Mauzy CA, Hwang O, Egloff AM, Wu LH, Chung FZ (July 1992). "Cloning, expression, and characterization of a gene encoding the human angiotensin II type 1A receptor". Biochemical and Biophysical Research Communications. 186 (1): 277–284. doi:10.1016/S0006-291X(05)80804-6. PMID 1378723.
• Curnow KM, Pascoe L, White PC (July 1992). "Genetic analysis of the human type-1 angiotensin II receptor". Molecular Endocrinology. 6 (7): 1113–1118. doi:10.1210/mend.6.7.1508224. PMID 1508224.
• Furuta H, Guo DF, Inagami T (February 1992). "Molecular cloning and sequencing of the gene encoding human angiotensin II type 1 receptor". Biochemical and Biophysical Research Communications. 183 (1): 8–13. doi:10.1016/0006-291X(92)91600-U. PMID 1543512.
• Takayanagi R, Ohnaka K, Sakai Y, Nakao R, Yanase T, Haji M, et al. (March 1992). "Molecular cloning, sequence analysis and expression of a cDNA encoding human type-1 angiotensin II receptor". Biochemical and Biophysical Research Communications. 183 (2): 910–916. doi:10.1016/0006-291X(92)90570-B. PMID 1550596.
• Bergsma DJ, Ellis C, Kumar C, Nuthulaganti P, Kersten H, Elshourbagy N, et al. (March 1992). "Cloning and characterization of a human angiotensin II type 1 receptor". Biochemical and Biophysical Research Communications. 183 (3): 989–995. doi:10.1016/S0006-291X(05)80288-8. PMID 1567413. S2CID 19816702.
• Gemmill RM, Drabkin HA (1992). "Report of the Second International Workshop on Human Chromosome 3 mapping". Cytogenetics and Cell Genetics. 57 (4): 162–166. doi:10.1159/000133138. PMID 1683828.
• Curnow KM, Pascoe L, Davies E, White PC, Corvol P, Clauser E (September 1995). "Alternatively spliced human type 1 angiotensin II receptor mRNAs are translated at different efficiencies and encode two receptor isoforms". Molecular Endocrinology. 9 (9): 1250–1262. doi:10.1210/mend.9.9.7491117. PMID 7491117. S2CID 46112700.
• Marrero MB, Schieffer B, Paxton WG, Heerdt L, Berk BC, Delafontaine P, Bernstein KE (May 1995). "Direct stimulation of Jak/STAT pathway by the angiotensin II AT1 receptor". Nature. 375 (6528): 247–250. Bibcode:1995Natur.375..247M. doi:10.1038/375247a0. PMID 7746328. S2CID 4272223.

External links

• "Angiotensin Receptors: AT₁". IUPHAR Database of Receptors and Ion Channels. International Union of Basic and Clinical Pharmacology. Archived from the original on 2014-02-28. Retrieved 2008-11-25.
• Human AGTR1 genome location and AGTR1 gene details page in the UCSC Genome Browser.