Biology:Angiotensin II receptor

From HandWiki
Short description: Class of G protein-coupled receptors
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

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

Receptor Mechanism[3]
AT1
AT2
  • Gi2 / 3
AT3
AT4

AT1

Main page: Biology: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 page: Biology: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

  • Angiotensin II receptor antagonist

References

  1. "International union of pharmacology. XXIII. The angiotensin II receptors". Pharmacological Reviews 52 (3): 415–72. September 2000. PMID 10977869. http://pharmrev.aspetjournals.org/cgi/content/abstract/52/3/415. 
  2. 2.0 2.1 "Angiotensin II signal transduction through the AT1 receptor: novel insights into mechanisms and pathophysiology". Clinical Science 112 (8): 417–28. April 2007. doi:10.1042/CS20060342. PMID 17346243. 
  3. Unless else specified in box, then ref is: Senselab
  4. "Angiotensin II receptors in the human brain". Regulatory Peptides 79 (1): 1–7. January 1999. doi:10.1016/S0167-0115(98)00138-4. PMID 9930578. 
  5. "The role of angiotensin II receptors in vascular regulation". Journal of Cardiovascular Pharmacology 6 (Suppl 4): S575-86. 1984. doi:10.1097/00005344-198406004-00004. PMID 6083400. 
  6. "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. doi:10.1161/01.HYP.0000193504.51489.cf. PMID 16286564. 
  7. "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. doi:10.1007/s10571-017-0533-x. PMID 28884431. 
  8. "AT4 receptor is insulin-regulated membrane aminopeptidase: potential mechanisms of memory enhancement". Trends in Endocrinology and Metabolism 14 (2): 72–7. March 2003. doi:10.1016/S1043-2760(02)00037-1. PMID 12591177. 
  9. "The angiotensin IV/AT4 receptor". Cellular and Molecular Life Sciences 61 (21): 2728–37. November 2004. doi:10.1007/s00018-004-4246-1. PMID 15549174. 
  10. "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. doi:10.1016/j.neuroscience.2005.10.051. PMID 16343778. 
  11. "From angiotensin IV binding site to AT4 receptor". Molecular and Cellular Endocrinology 302 (2): 159–66. April 2009. doi:10.1016/j.mce.2008.11.015. PMID 19071192. 
  12. "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. doi:10.1007/s00213-010-1791-1. PMID 20224888. 
  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. "Brain renin-angiotensin--a new look at an old system". Progress in Neurobiology 95 (1): 49–67. September 2011. doi:10.1016/j.pneurobio.2011.07.001. PMID 21777652. 
  15. "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. doi:10.1124/jpet.111.182220. PMID 21719467. 

External links