Angiotensin II receptor explained

angiotensin II receptor, type 1
Hgncid:336
Symbol:AGTR1
Altsymbols:AGTR1B
Iuphar Id:yes
Entrezgene:185
Omim:106165
Refseq:NM_000685
Uniprot:P30556
Chromosome:3
Arm:q
Band:21
Locussupplementarydata:-q25
angiotensin II receptor, type 2
Hgncid:338
Symbol:AGTR2
Iuphar Id:yes
Entrezgene:186
Omim:300034
Refseq:NM_000686
Uniprot:P50052
Chromosome:X
Arm:q
Band:22
Locussupplementarydata:-q23

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]

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

ReceptorMechanism[3]
AT1
AT2
  • Gi2 / 3
AT3
AT4

AT1

See 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.

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

See 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

Notes and References

  1. de Gasparo M, Catt KJ, Inagami T, Wright JW, Unger T . International union of pharmacology. XXIII. The angiotensin II receptors . Pharmacological Reviews . 52 . 3 . 415–72 . September 2000 . 10977869 .
  2. Higuchi S, Ohtsu H, Suzuki H, Shirai H, Frank GD, Eguchi S . Angiotensin II signal transduction through the AT1 receptor: novel insights into mechanisms and pathophysiology . Clinical Science . 112 . 8 . 417–28 . April 2007 . 17346243 . 10.1042/CS20060342 . 27624282 .
  3. Unless else specified in box, then ref is: Senselab
  4. Allen AM, MacGregor DP, McKinley MJ, Mendelsohn FA . Angiotensin II receptors in the human brain . Regulatory Peptides . 79 . 1 . 1–7 . January 1999 . 9930578 . 10.1016/S0167-0115(98)00138-4 . 21317534 .
  5. Catt KJ, Mendelsohn FA, Millan MA, Aguilera G . The role of angiotensin II receptors in vascular regulation . Journal of Cardiovascular Pharmacology . 6 . Suppl 4 . S575-86 . 1984 . 6083400 . 10.1097/00005344-198406004-00004 . free .
  6. D'Amore A, Black MJ, Thomas WG . 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 . December 2005 . 16286564 . 10.1161/01.HYP.0000193504.51489.cf . 10812400 .
  7. Saavedra JM, Armando I . Angiotensin II AT2 Receptors Contribute to Regulate the Sympathoadrenal and Hormonal Reaction to Stress Stimuli . Cellular and Molecular Neurobiology . 38 . 1 . 85–108 . January 2018 . 28884431 . 6668356 . 10.1007/s10571-017-0533-x .
  8. Albiston AL, Mustafa T, McDowall SG, Mendelsohn FA, Lee J, Chai SY . AT4 receptor is insulin-regulated membrane aminopeptidase: potential mechanisms of memory enhancement . Trends in Endocrinology and Metabolism . 14 . 2 . 72–7 . March 2003 . 12591177 . 10.1016/S1043-2760(02)00037-1 . 6481079 .
  9. Chai SY, Fernando R, Peck G, Ye SY, Mendelsohn FA, Jenkins TA, Albiston AL . The angiotensin IV/AT4 receptor . Cellular and Molecular Life Sciences . 61 . 21 . 2728–37 . November 2004 . 15549174 . 10.1007/s00018-004-4246-1 . 22816307 .
  10. Davis CJ, Kramár EA, De A, Meighan PC, Simasko SM, Wright JW, Harding JW . 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 . 2006 . 16343778 . 10.1016/j.neuroscience.2005.10.051 . 8280334 .
  11. Vanderheyden PM . From angiotensin IV binding site to AT4 receptor . Molecular and Cellular Endocrinology . 302 . 2 . 159–66 . April 2009 . 19071192 . 10.1016/j.mce.2008.11.015 . 140205109 .
  12. Beyer CE, Dwyer JM, Platt BJ, Neal S, Luo B, Ling HP, Lin Q, Mark RJ, Rosenzweig-Lipson S, Schechter LE . 6 . Angiotensin IV elevates oxytocin levels in the rat amygdala and produces anxiolytic-like activity through subsequent oxytocin receptor activation . Psychopharmacology . 209 . 4 . 303–11 . May 2010 . 20224888 . 10.1007/s00213-010-1791-1 . 7892428 . John Dwyer (medicine) .
  13. Ph.D. . Design and Synthesis of Angiotensin IV Peptidomimetics Targeting the Insulin-Regulated Aminopeptidase (IRAP) . Andersson H . 2010 . Uppsala Universitet . 2012-01-08 .
  14. Wright JW, Harding JW . Brain renin-angiotensin--a new look at an old system . Progress in Neurobiology . 95 . 1 . 49–67 . September 2011 . 21777652 . 10.1016/j.pneurobio.2011.07.001 . 25955824 .
  15. Benoist CC, Wright JW, Zhu M, Appleyard SM, Wayman GA, Harding JW . 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 . October 2011 . 21719467 . 3186286 . 10.1124/jpet.111.182220 .

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