Odtnhj

AGT
Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 4FYS, 1N9U, 1N9V, 2JP8, 2WXW, 2X0B, 3CK0, 3WOO, 3WOR, 4AA1, 4APH, 5E2Q
Identifiers
Aliases	AGT, ANHU, SERPINA8, angiotensinogen, hFLT1
External IDs	MGI: 87963 HomoloGene: 14 GeneCards: AGT
Gene location (Human) Chr. Chromosome 1 (human)[1] Band 1q42.2 Start 230,702,523 bp[1] End 230,714,297 bp[1]
Gene location (Mouse) Chr. Chromosome 8 (mouse)[2] Band 8 E2|8 72.81 cM Start 124,556,534 bp[2] End 124,569,706 bp[2]
RNA expression pattern More reference expression data
Gene ontology Molecular function • type 1 angiotensin receptor binding • hormone activity • superoxide-generating NADPH oxidase activator activity • growth factor activity • type 2 angiotensin receptor binding • protein binding • sodium channel regulator activity • serine-type endopeptidase inhibitor activity • angiotensin receptor binding • receptor ligand activity Cellular component • cytoplasm • extracellular exosome • blood microparticle • extracellular space • cytosol • extracellular region • collagen-containing extracellular matrix Biological process • uterine smooth muscle contraction • renal system process • regulation of extracellular matrix assembly • GO:0042310 vasoconstriction • positive regulation of cholesterol esterification • positive regulation of catalytic activity • positive regulation of cardiac muscle hypertrophy • phospholipase C-activating G-protein coupled receptor signaling pathway • cell surface receptor signaling pathway • cellular response to mechanical stimulus • blood vessel remodeling • positive regulation of reactive oxygen species metabolic process • stress-activated MAPK cascade • artery smooth muscle contraction • positive regulation of extrinsic apoptotic signaling pathway • regulation of systemic arterial blood pressure by renin-angiotensin • regulation of apoptotic process • positive regulation of cellular protein metabolic process • regulation of blood vessel size • negative regulation of neurotrophin TRK receptor signaling pathway • positive regulation of branching involved in ureteric bud morphogenesis • regulation of long-term neuronal synaptic plasticity • positive regulation of renal sodium excretion • kidney development • positive regulation of fibroblast proliferation • cellular sodium ion homeostasis • ERK1 and ERK2 cascade • activation of phospholipase C activity • angiotensin maturation • positive regulation of extracellular matrix constituent secretion • positive regulation of transcription, DNA-templated • positive regulation of blood pressure • negative regulation of cell growth • positive regulation of peptidyl-tyrosine phosphorylation • regulation of norepinephrine secretion • positive regulation of inflammatory response • catenin import into nucleus • female pregnancy • positive regulation of protein tyrosine kinase activity • negative regulation of tissue remodeling • regulation of heart rate • regulation of blood pressure • positive regulation of macrophage derived foam cell differentiation • regulation of vasoconstriction • positive regulation of NF-kappaB transcription factor activity • positive regulation of NAD(P)H oxidase activity • nitric oxide mediated signal transduction • G-protein coupled receptor signaling pathway coupled to cGMP nucleotide second messenger • smooth muscle cell proliferation • positive regulation of epidermal growth factor receptor signaling pathway • regulation of blood volume by renin-angiotensin • regulation of cardiac conduction • regulation of calcium ion transport • regulation of transmission of nerve impulse • regulation of blood vessel diameter by renin-angiotensin • cell growth involved in cardiac muscle cell development • regulation of renal sodium excretion • positive regulation of cytokine production • positive regulation of membrane hyperpolarization • response to muscle activity involved in regulation of muscle adaptation • negative regulation of sodium ion transmembrane transporter activity • positive regulation of nitric oxide biosynthetic process • cytokine secretion • angiotensin-mediated drinking behavior • cell-cell signaling • renin-angiotensin regulation of aldosterone production • aging • GO:0042311 vasodilation • positive regulation of endothelial cell migration • low-density lipoprotein particle remodeling • regulation of cell proliferation • regulation of cell growth • positive regulation of cell proliferation • fibroblast proliferation • negative regulation of angiogenesis • positive regulation of gap junction assembly • positive regulation of phosphatidylinositol 3-kinase signaling • positive regulation of superoxide anion generation • positive regulation of L-lysine import across plasma membrane • positive regulation of glucose import in response to insulin stimulus • positive regulation of cardiac muscle cell apoptotic process • angiotensin-activated signaling pathway • positive regulation of vascular smooth muscle cell proliferation • positive regulation of cytosolic calcium ion concentration • negative regulation of gene expression • regulation of renal output by angiotensin • negative regulation of endopeptidase activity • positive regulation of vascular associated smooth muscle cell migration • regulation of molecular function • positive regulation of activation of Janus kinase activity • regulation of lipid metabolic process • positive regulation of blood vessel diameter • positive regulation of L-arginine import across plasma membrane • regulation of receptor activity • G-protein coupled receptor signaling pathway • positive regulation of neuron projection development • response to estradiol • cellular response to angiotensin • protein import into nucleus • associative learning • operant conditioning • positive regulation of insulin receptor signaling pathway Sources:Amigo / QuickGO
Orthologs
Species	Human	Mouse
Entrez	183	11606
Ensembl	ENSG00000135744	ENSMUSG00000031980
UniProt	P01019	P11859 Q3UTR7
RefSeq (mRNA)	NM_000029	NM_007428
RefSeq (protein)	NP_000020	NP_031454
Location (UCSC)	Chr 1: 230.7 – 230.71 Mb	Chr 8: 124.56 – 124.57 Mb
PubMed search	[3]	[4]
Wikidata
View/Edit Human View/Edit Mouse

Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the adrenal cortex to promote sodium retention by the kidneys.

An oligopeptide, angiotensin is a hormone and a dipsogen. It is derived from the precursor molecule angiotensinogen, a serum globulin produced in the liver. Angiotensin was isolated in the late 1930s (first named 'angiotonin' or 'hypertensin') and subsequently characterized and synthesized by groups at the Cleveland Clinic and Ciba laboratories.^[5]

Precursor and types

Angiotensinogen

Angiotensinogen is an α-2-globulin produced constitutively and released into the circulation mainly by the liver. It is a member of the serpin family, although it is not known to inhibit other enzymes, unlike most serpins. Plasma angiotensinogen levels are increased by plasma corticosteroid, estrogen, thyroid hormone, and angiotensin II levels.

Angiotensinogen is also known as renin substrate. Human angiotensinogen is 452 amino acids long, but other species have angiotensinogen of varying sizes. The first 12 amino acids are the most important for activity.

Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Val-Ile-...

Angiotensin I

Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu | Val-Ile-...

Renin–angiotensin–aldosterone system

Angiotensin I (CAS# 11128-99-7), officially called proangiotensin, is formed by the action of renin on angiotensinogen. Renin cleaves the peptide bond between the leucine (Leu) and valine (Val) residues on angiotensinogen, creating the decapeptide (ten amino acid) (des-Asp) angiotensin I. Renin is produced in the kidneys in response to renal sympathetic activity, decreased intrarenal blood pressure (<90mmHg systolic blood pressure^[6] ) at the juxtaglomerular cells, or decreased delivery of Na+ and Cl- to the macula densa.^[7] If a reduced NaCl concentration^[8] in the distal tubule is sensed by the macula densa, renin release by juxtaglomerular cells is increased. This sensing mechanism for macula densa-mediated renin secretion appears to have a specific dependency on chloride ions rather than sodium ions. Studies using isolated preparations of thick ascending limb with glomerulus attached in low NaCl perfusate were unable to inhibit renin secretion when various sodium salts were added but could inhibit renin secretion with the addition of chloride salts.^[9] This, and similar findings obtained in vivo,^[10] has led some to believe that perhaps "the initiating signal for MD control of renin secretion is a change in the rate of NaCl uptake predominantly via a luminal Na,K,2Cl co-transporter whose physiological activity is determined by a change in luminal Cl concentration."^[11]

Angiotensin I appears to have no direct biological activity and exists solely as a precursor to angiotensin II.

Angiotensin II

Asp-Arg-Val-Tyr-Ile-His-Pro-Phe

Angiotensin I is converted to angiotensin II (AII) through removal of two C-terminal residues by the enzyme angiotensin-converting enzyme (ACE), primarily through ACE within the lung (but also present in endothelial cells, kidney epithelial cells, and the brain). Angiotensin II acts on the CNS to increase vasopressin production, and also acts on venous and arterial smooth muscle to cause vasoconstriction. Angiotensin II also increases aldosterone secretion, therefore, it acts as an endocrine, autocrine/paracrine, and intracrine hormone.

ACE is a target of ACE inhibitor drugs, which decrease the rate of angiotensin II production. Angiotensin II increases blood pressure by stimulating the Gq protein in vascular smooth muscle cells (which in turn activates an IP3-dependent mechanism leading to a rise in intracellular calcium levels and ultimately causing contraction). In addition, angiotensin II acts at the Na⁺/H⁺ exchanger in the proximal tubules of the kidney to stimulate Na reabsorption and H⁺ excretion which is coupled to bicarbonate reabsorption. This ultimately results in an increase in blood volume, pressure, and pH.^[12] Hence, ACE inhibitors are major anti-hypertensive drugs.

Other cleavage products of ACE, seven or 9 amino acids long, are also known; they have differential affinity for angiotensin receptors, although their exact role is still unclear. The action of AII itself is targeted by angiotensin II receptor antagonists, which directly block angiotensin II AT₁ receptors.

Angiotensin II is degraded to angiotensin III by angiotensinases located in red blood cells and the vascular beds of most tissues. It has a half-life in circulation of around 30 seconds, whereas, in tissue, it may be as long as 15–30 minutes.

Angiotensin II results in increased inotropy, chronotropy, catecholamine (norepinephrine) release, catecholamine sensitivity, aldosterone levels, vasopressin levels, and cardiac remodeling and vasoconstriction through AT1 receptors on peripheral vessels (conversely, AT2 receptors impair cardiac remodeling). This is why ACE inhibitors and ARBs help to prevent remodeling that occurs secondary to angiotensin II and are beneficial in CHF. ^[11]

Angiotensin III

Asp | Arg-Val-Tyr-Ile-His-Pro-Phe

Angiotensin III has 40% of the pressor activity of angiotensin II, but 100% of the aldosterone-producing activity.
Increases mean arterial pressure.

Angiotensin IV

Arg | Val-Tyr-Ile-His-Pro-Phe

Angiotensin IV is a hexapeptide that, like angiotensin III, has some lesser activity. Angiotensin IV has a wide range of activities in the central nervous system.^[13][14]

The exact identity of AT4 receptors has not been established. There is evidence that the AT4 receptor is insulin-regulated aminopeptidase (IRAP).^[15] There is also evidence that angiotensin IV interacts with the HGF system through the c-Met receptor.^[16][17]

Synthetic small molecule analogues of angiotensin IV with the ability to penetrate through blood brain barrier have been developed.^[17]

Effects

See also Renin–angiotensin system#Effects

Angiotensins II, III and IV have a number of effects throughout the body:

Adipic

Angiotensins "modulate fat mass expansion through upregulation of adipose tissue lipogenesis ... and downregulation of lipolysis " ^[18]

Cardiovascular

They are potent direct vasoconstrictors, constricting arteries and veins and increasing blood pressure. This effect is achieved through activation of the GPCR AT1, which signals through a Gq protein to activate Phospholipase C, and subsequently increase intracellular calcium.^[19]

Angiotensin II has prothrombotic potential through adhesion and aggregation of platelets and stimulation of PAI-1 and PAI-2.^[20][21]

When cardiac cell growth is stimulated, a local (autocrine-paracrine) renin–angiotensin system is activated in the cardiac myocyte, which stimulates cardiac cell growth through protein kinase C. The same system can be activated in smooth muscle cells in conditions of hypertension, atherosclerosis, or endothelial damage. Angiotensin II is the most important Gq stimulator of the heart during hypertrophy, compared to endothelin-1 and α1 adrenoreceptors.^{[citation needed]}

Neural

Angiotensin II increases thirst sensation (dipsogen) through the area postrema and subfornical organ of the brain,^[22][23][24] decreases the response of the baroreceptor reflex, increases the desire for salt, increases secretion of ADH from the posterior pituitary, and increases secretion of ACTH from the anterior pituitary.^[22] It also potentiates the release of norepinephrine by direct action on postganglionic sympathetic fibers.^{[citation needed]}

Adrenal

Angiotensin II acts on the adrenal cortex, causing it to release aldosterone, a hormone that causes the kidneys to retain sodium and lose potassium. Elevated plasma angiotensin II levels are responsible for the elevated aldosterone levels present during the luteal phase of the menstrual cycle.

Renal

Angiotensin II has a direct effect on the proximal tubules to increase Na⁺reabsorption. It has a complex and variable effect on glomerular filtration and renal blood flow depending on the setting. Increases in systemic blood pressure will maintain renal perfusion pressure; however, constriction of the afferent and efferent glomerular arterioles will tend to restrict renal blood flow. The effect on the efferent arteriolar resistance is, however, markedly greater, in part due to its smaller basal diameter; this tends to increase glomerular capillary hydrostatic pressure and maintain glomerular filtration rate. A number of other mechanisms can affect renal blood flow and GFR. High concentrations of Angiotensin II can constrict the glomerular mesangium, reducing the area for glomerular filtration. Angiotensin II is a sensitizer to tubuloglomerular feedback, preventing an excessive rise in GFR. Angiotensin II causes the local release of prostaglandins, which, in turn, antagonize renal vasoconstriction. The net effect of these competing mechanisms on glomerular filtration will vary with the physiological and pharmacological environment.

See also

References

Further reading

External links

Wikimedia Commons has media related to Angiotensin.

• The MEROPS online database for peptidases and their inhibitors: I04.953
  


• 
  Angiotensins at the US National Library of Medicine Medical Subject Headings (MeSH)


• Human AGT genome location and AGT gene details page in the UCSC Genome Browser.