Angiotensin receptor

angiotensin II receptor, type 1
Identifiers
Symbol	AGTR1
Alt. symbols	AGTR1B
IUPHAR	34
Entrez	185
HUGO	336
OMIM	106165
RefSeq	NM_000685
UniProt	P30556
Other data
Locus	Chr. 3 q21-q25

angiotensin II receptor, type 2
Identifiers
Symbol	AGTR2
IUPHAR	35
Entrez	186
HUGO	338
OMIM	300034
RefSeq	NM_000686
UniProt	P50052
Other data
Locus	Chr. X q22-q23

The angiotensin receptors are a class of G protein-coupled receptors with angiotensin II as their ligands.^[1] They are important in the renin-angiotensin system: they are responsible for the signal transduction of the vasoconstricting stimulus of the main effector hormone, angiotensin II.^[2]

Structure

The AT₁ and AT₂ receptors share a sequence identity of ~30%, but have a similar affinity for angiotensin II, which is their main ligand.

Members

Overview table

Receptor	Mechanism[3]
AT1	Gq/11 Gi/o
AT2	Gi2 / 3
AT3
AT4

Losartan is a selective AT1 antagonist,while PD123177 is a selective AT2 antagonist.Both subtypes are G-protein coupled receptor.

AT₁

The AT₁ receptor is the best elucidated angiotensin receptor.

Location within the body

The AT1 subtype is found in the heart, blood vessels, kidney, adrenal cortex, lung and brain and mediates the vasoconstrictor effects.

Mechanism

The angiotensin receptor is activated by the vasoconstricting peptide angiotensin II. The activated receptor in turn couples to G_q/11 and G_i/o 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 and activates various tyrosine kinases.^[2]

Effects

Effects mediated by the AT₁ receptor 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.^[4]

AT₂

AT₂ receptors are more plentiful in the fetus and neonate. The AT₂ receptor remains enigmatic and controversial – is probably involved in vascular growth. Effects mediated by the AT₂ receptor are suggested to include inhibition of cell growth, fetal tissue development, modulation of extracellular matrix, neuronal regeneration, apoptosis, cellular differentiation, and maybe vasodilation and left ventricular hypertrophy.^[5]

AT₃ and AT₄

Other poorly characterized subtypes include the AT₃ and AT₄ receptors. The AT₄ receptor is activated by the angiotensin II metabolite angiotensin IV, and may play a role in regulation of the CNS extracellular matrix, as well as modulation of oxytocin release.^{[6][7][8][9][10][11][12][13]}

See also

• Angiotensin II receptor antagonist

References

1. de Gasparo M, Catt KJ, Inagami T, Wright JW, Unger T (2000). "International union of pharmacology. XXIII. The angiotensin II receptors". Pharmacol. Rev. 52 (3): 415–72. PMID 10977869.
2. Higuchi S, Ohtsu H, Suzuki H, Shirai H, Frank GD, Eguchi S (2007). "Angiotensin II signal transduction through the AT1 receptor: novel insights into mechanisms and pathophysiology". Clin. Sci. 112 (8): 417–28. doi:10.1042/CS20060342. PMID 17346243.
3. Unless else specified in box, then ref is: Senselab
4. Catt KJ, Mendelsohn FA, Millan MA, Aguilera G (1984). "The role of angiotensin II receptors in vascular regulation". J. Cardiovasc. Pharmacol. 6 (Suppl 4): S575–86. doi:10.1097/00005344-198406004-00004. PMID 6083400.
5. D'Amore A, Black MJ, Thomas WG (December 2005). "The angiotensin II type 2 receptor causes constitutive growth of cardiomyocytes and does not antagonize angiotensin II type 1 receptor-mediated hypertrophy however they do imply that myocardial infarction increase hypertension in arthritis with hyperkalemia". Hypertension 46 (6): 1347–54. doi:10.1161/01.HYP.0000193504.51489.cf. PMID 16286564.
6. Albiston AL, Mustafa T, McDowall SG, Mendelsohn FA, Lee J, Chai SY (March 2003). "AT4 receptor is insulin-regulated membrane aminopeptidase: potential mechanisms of memory enhancement". Trends Endocrinol. Metab. 14 (2): 72–7. doi:10.1016/S1043-2760(02)00037-1. PMID 12591177.
7. Chai SY, Fernando R, Peck G, Ye SY, Mendelsohn FA, Jenkins TA, Albiston AL (November 2004). "The angiotensin IV/AT4 receptor". Cell. Mol. Life Sci. 61 (21): 2728–37. doi:10.1007/s00018-004-4246-1. PMID 15549174.
8. Davis CJ, Kramár EA, De A, Meighan PC, Simasko SM, Wright JW, Harding JW (2006). "AT4 receptor activation increases intracellular calcium influx and induces a non-N-methyl-D-aspartate dependent form of long-term potentiation". Neuroscience 137 (4): 1369–79. doi:10.1016/j.neuroscience.2005.10.051. PMID 16343778.
9. Vanderheyden PM (April 2009). "From angiotensin IV binding site to AT4 receptor". Mol. Cell. Endocrinol. 302 (2): 159–66. doi:10.1016/j.mce.2008.11.015. PMID 19071192.
10. Beyer CE, Dwyer JM, Platt BJ, Neal S, Luo B, Ling HP, Lin Q, Mark RJ, Rosenzweig-Lipson S, Schechter LE (May 2010). "Angiotensin IV elevates oxytocin levels in the rat amygdala and produces anxiolytic-like activity through subsequent oxytocin receptor activation". Psychopharmacology (Berl.) 209 (4): 303–11. doi:10.1007/s00213-010-1791-1. PMID 20224888.
11. Andersson H (2010). Design and Synthesis of Angiotensin IV Peptidomimetics Targeting the Insulin-Regulated Aminopeptidase (IRAP) (Ph.D. thesis). Uppsala Universitet. Retrieved 2012-01-08.
12. Wright JW, Harding JW (September 2011). "Brain renin-angiotensin—a new look at an old system". Prog. Neurobiol. 95 (1): 49–67. doi:10.1016/j.pneurobio.2011.07.001. PMID 21777652.
13. Benoist CC, Wright JW, Zhu M, Appleyard SM, Wayman GA, Harding JW (October 2011). "Facilitation of hippocampal synaptogenesis and spatial memory by C-terminal truncated Nle1-angiotensin IV analogs". J. Pharmacol. Exp. Ther. 339 (1): 35–44. doi:10.1124/jpet.111.182220. PMC 3186286. PMID 21719467.

External links

• Receptors, Angiotensin at the US National Library of Medicine Medical Subject Headings (MeSH)