“Angiotensin II receptor type 1”的意思、由来-开放百科全书

Angiotensin II receptor type 1 or AT₁ receptor is the best characterized angiotensin receptor. It has vasopressor effects and regulates aldosterone secretion. It is an important effector controlling blood pressure and volume in the cardiovascular system. Angiotensin II receptor antagonists are drugs indicated for hypertension, diabetic nephropathy and congestive heart failure.

Function

The AT₁ receptor mediates the major cardiovascular effects of angiotensin II. Effects 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.^[1]

Mechanism

The angiotensin receptor is activated by the vasoconstricting peptide angiotensin II. The activated receptor in turn couples to G_q/11 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]

Clinical significance

The AT₁ receptor may play role in the generation of reperfusion arrhythmias following restoration of blood flow to ischemic or infarcted myocardium.{{citation needed|date=November 2015}}

The AT₁ receptor has also been implicated in post-traumatic stress disorder,^[3]{{Unreliable medical source|date=October 2015|sure=y}}

Animal studies

AT₁ receptor antagonists have been shown to reduce fear memory recall in mice.^[4]^[5]

Gene

It was previously thought that a related gene, denoted as AGTR1B, existed; however, it is now believed that there is only one type 1 receptor gene in humans. At least four transcript variants have been described for this gene. Additional variants have been described but their full-length nature has not been determined. The entire coding sequence is contained in the terminal exon and is present in all transcript variants.^[6]

Interactions

Angiotensin II receptor type 1 has been shown to interact with Zinc finger and BTB domain-containing protein 16.^[7] The protein's mRNA has been reported to interact with Mir-132 microRNA as part of an RNA silencing mechanism that reduces receptor expression.^[8]

References

1. ^{{cite journal | vauthors = Catt KJ, Mendelsohn FA, Millan MA, Aguilera G | title = The role of angiotensin II receptors in vascular regulation | journal = Journal of Cardiovascular Pharmacology | volume = 6 Suppl 4 | issue = Suppl 4 | pages = S575-86 | year = 1984 | pmid = 6083400 | doi = 10.1097/00005344-198406004-00004 }}
2. ^{{cite journal | vauthors = Higuchi S, Ohtsu H, Suzuki H, Shirai H, Frank GD, Eguchi S | title = Angiotensin II signal transduction through the AT1 receptor: novel insights into mechanisms and pathophysiology | journal = Clinical Science | volume = 112 | issue = 8 | pages = 417–28 | date = Apr 2007 | pmid = 17346243 | doi = 10.1042/CS20060342 }}
3. ^{{cite journal | vauthors = Khoury NM, Marvar PJ, Gillespie CF, Wingo A, Schwartz A, Bradley B, Kramer M, Ressler KJ | title = The renin-angiotensin pathway in posttraumatic stress disorder: angiotensin-converting enzyme inhibitors and angiotensin receptor blockers are associated with fewer traumatic stress symptoms | journal = The Journal of Clinical Psychiatry | volume = 73 | issue = 6 | pages = 849–55 | date = Jun 2012 | pmid = 22687631 | pmc = 4087173 | doi = 10.4088/JCP.11m07316 }}
4. ^{{cite journal | vauthors = Marvar PJ, Goodman J, Fuchs S, Choi DC, Banerjee S, Ressler KJ | title = Angiotensin type 1 receptor inhibition enhances the extinction of fear memory | journal = Biological Psychiatry | volume = 75 | issue = 11 | pages = 864–72 | date = Jun 2014 | pmid = 24094510 | pmc = 3975818 | doi = 10.1016/j.biopsych.2013.08.024 }}
5. ^{{cite journal | vauthors = Hurt RC, Garrett JC, Keifer OP, Linares A, Couling L, Speth RC, Ressler KJ, Marvar PJ | title = Angiotensin type 1a receptors on corticotropin-releasing factor neurons contribute to the expression of conditioned fear(1) | journal = Genes, Brain, and Behavior | volume = 14 | issue = 7 | pages = 526–33 | date = Sep 2015 | pmid = 26257395 | doi = 10.1111/gbb.12235 | pmc = 4573765 }}
6. ^{{cite web | title = Entrez Gene: AGTR1 angiotensin II receptor, type 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=185| accessdate = }}
7. ^{{cite journal | vauthors = Senbonmatsu T, Saito T, Landon EJ, Watanabe O, Price E, Roberts RL, Imboden H, Fitzgerald TG, Gaffney FA, Inagami T | title = A novel angiotensin II type 2 receptor signaling pathway: possible role in cardiac hypertrophy | journal = The EMBO Journal | volume = 22 | issue = 24 | pages = 6471–82 | date = Dec 2003 | pmid = 14657020 | pmc = 291832 | doi = 10.1093/emboj/cdg637 }}
8. ^{{cite journal |vauthors =Elton TS, Kuhn DE, Malana GE, Martin MM, Nuovo GJ, Pleister AP, Feldman DS |title=MiR-132 Regulates Angiotensin II Type 1 Receptor Expression Through a Protein Coding Region Binding Site|journal=Circulation|volume=118 |issue=18 |pages=S513|year=2007|url=http://circ.ahajournals.org/cgi/content/meeting_abstract/118/18_MeetingAbstracts/S_513}}