Angiotensin II receptor

The angiotensin II receptors, (ATR1) and (ATR2), 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]

angiotensin II receptor, type 1
Identifiers
SymbolAGTR1
Alt. symbolsAGTR1B
IUPHAR34
NCBI gene185
HGNC336
OMIM106165
RefSeqNM_000685
UniProtP30556
Other data
LocusChr. 3 q21-q25
angiotensin II receptor, type 2
Identifiers
SymbolAGTR2
IUPHAR35
NCBI gene186
HGNC338
OMIM300034
RefSeqNM_000686
UniProtP50052
Other data
LocusChr. X q22-q23

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
AT2
AT3
AT4

AT1
Main article: Angiotensin II receptor type 1

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 circumventricular organs of brain, basal ganglia, brainstem[4] and mediates the vasoconstrictor effects.

Mechanism

The angiotensin receptor is activated by the vasoconstricting peptide angiotensin II. The activated receptor in turn couples to Gq/11 and Gi/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.[5]

AT2
Main article: Angiotensin II receptor type 2

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.[6] In humans the AT2 subtype is found in molecular layer of the cerebellum. In the mouse is found in the adrenal gland, amygdaloid nuclei and, in small numbers, in the paraventricular nucleus of the hypothalamus and the locus coeruleus.[7]

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.[8][9][10][11][12][13][14][15]

See also

References
  1. de Gasparo M, Catt KJ, Inagami T, Wright JW, Unger T (September 2000). "International union of pharmacology. XXIII. The angiotensin II receptors". Pharmacological Reviews. 52 (3): 415–72. PMID 10977869.
  2. Higuchi S, Ohtsu H, Suzuki H, Shirai H, Frank GD, Eguchi S (April 2007). "Angiotensin II signal transduction through the AT1 receptor: novel insights into mechanisms and pathophysiology". Clinical Science. 112 (8): 417–28. doi:10.1042/CS20060342. PMID 17346243.
  3. Unless else specified in box, then ref is: Senselab Archived 2009-02-28 at the Wayback Machine
  4. Allen AM, MacGregor DP, McKinley MJ, Mendelsohn FA (January 1999). "Angiotensin II receptors in the human brain". Regulatory Peptides. 79 (1): 1–7. doi:10.1016/S0167-0115(98)00138-4. PMID 9930578. S2CID 21317534.
  5. Catt KJ, Mendelsohn FA, Millan MA, Aguilera G (1984). "The role of angiotensin II receptors in vascular regulation". Journal of Cardiovascular Pharmacology. 6 Suppl 4 (Suppl 4): S575-86. doi:10.1097/00005344-198406004-00004. PMID 6083400.
  6. 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". Hypertension. 46 (6): 1347–54. doi:10.1161/01.HYP.0000193504.51489.cf. PMID 16286564.
  7. Saavedra JM, Armando I (January 2018). "Angiotensin II AT2 Receptors Contribute to Regulate the Sympathoadrenal and Hormonal Reaction to Stress Stimuli". Cellular and Molecular Neurobiology. 38 (1): 85–108. doi:10.1007/s10571-017-0533-x. PMC 6668356. PMID 28884431.
  8. 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 in Endocrinology and Metabolism. 14 (2): 72–7. doi:10.1016/S1043-2760(02)00037-1. PMID 12591177. S2CID 6481079.
  9. Chai SY, Fernando R, Peck G, Ye SY, Mendelsohn FA, Jenkins TA, Albiston AL (November 2004). "The angiotensin IV/AT4 receptor". Cellular and Molecular Life Sciences. 61 (21): 2728–37. doi:10.1007/s00018-004-4246-1. PMID 15549174.
  10. 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. S2CID 8280334.
  11. Vanderheyden PM (April 2009). "From angiotensin IV binding site to AT4 receptor". Molecular and Cellular Endocrinology. 302 (2): 159–66. doi:10.1016/j.mce.2008.11.015. PMID 19071192. S2CID 140205109.
  12. Beyer CE, Dwyer JM, Platt BJ, Neal S, Luo B, Ling HP, et al. (May 2010). "Angiotensin IV elevates oxytocin levels in the rat amygdala and produces anxiolytic-like activity through subsequent oxytocin receptor activation". Psychopharmacology. 209 (4): 303–11. doi:10.1007/s00213-010-1791-1. PMID 20224888. S2CID 7892428.
  13. 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.
  14. Wright JW, Harding JW (September 2011). "Brain renin-angiotensin--a new look at an old system". Progress in Neurobiology. 95 (1): 49–67. doi:10.1016/j.pneurobio.2011.07.001. PMID 21777652. S2CID 25955824.
  15. 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". The Journal of Pharmacology and Experimental Therapeutics. 339 (1): 35–44. doi:10.1124/jpet.111.182220. PMC 3186286. PMID 21719467.
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