Angiotensin

Source: Wikipedia, the free encyclopedia.
(Redirected from
Angiotensinogen
)
angiotensins
Ensembl
UniProt
RefSeq (mRNA)

n/a

n/a

RefSeq (protein)

n/a

n/a

Location (UCSC)n/an/a
PubMed searchn/an/a
Wikidata
View/Edit Human

Angiotensin is a peptide hormone that causes vasoconstriction and an increase in blood pressure. It is part of the renin–angiotensin system, which regulates blood pressure. Angiotensin also stimulates the release of aldosterone from the adrenal cortex to promote sodium retention by the kidneys.

An oligopeptide, angiotensin is a hormone and a dipsogen. It is derived from the precursor molecule angiotensinogen, a serum globulin produced in the liver. Angiotensin was isolated in the late 1930s (first named 'angiotonin' or 'hypertensin') and subsequently characterized and synthesized by groups at the Cleveland Clinic and Ciba laboratories.[1]

Precursor and types

Angiotensinogen

Crystal structure of reactive center loop cleaved angiotensinogen via x-ray diffraction
AGT
Available structures
Gene ontology
Molecular function
Cellular component
Biological process
Sources:Amigo / QuickGO
Ensembl
UniProt
RefSeq (mRNA)

NM_000029
NM_001382817
NM_001384479

NM_007428

RefSeq (protein)

NP_000020
NP_001369746

NP_031454

Location (UCSC)Chr 1: 230.69 – 230.75 MbChr 8: 125.28 – 125.3 Mb
PubMed search[4][5]
Wikidata
View/Edit HumanView/Edit Mouse

Angiotensinogen is an α-2-globulin synthesized in the liver[6] and is a precursor for angiotensin, but has also been indicated as having many other roles not related to angiotensin peptides.[7] It is a member of the serpin family of proteins, leading to another name: Serpin A8,[8] although it is not known to inhibit other enzymes like most serpins. In addition, a generalized crystal structure can be estimated by examining other proteins of the serpin family, but angiotensinogen has an elongated N-terminus compared to other serpin family proteins.[9] Obtaining actual crystals for X-ray diffractometric analysis is difficult in part due to the variability of glycosylation that angiotensinogen exhibits. The non-glycosylated and fully glycosylated states of angiotensinogen also vary in molecular weight, the former weighing 53 kDa and the latter weighing 75 kDa, with a plethora of partially glycosylated states weighing in between these two values.[7]

Angiotensinogen is also known as renin substrate. It is cleaved at the N-terminus by renin to result in angiotensin I, which will later be modified to become angiotensin II.[7][9] This peptide is 485 amino acids long, and 10 N-terminus amino acids are cleaved when renin acts on it.[7] The first 12 amino acids are the most important for activity.

Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu-Val-Ile-...[clarification needed]

Plasma angiotensinogen levels are increased by plasma corticosteroid, estrogen, thyroid hormone, and angiotensin II levels. In mice with a full body deficit of angiotensinogen, the effects observed were low newborn survival rate, stunted body weight gain, stunted growth, and abnormal renal development.[7]

Angiotensin I

Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-His-Leu | Val-Ile-...[clarification needed]
Renin–angiotensin–aldosterone system

Angiotensin I (

Na,K,2Cl co-transporter whose physiological activity is determined by a change in luminal Cl concentration."[15]

Angiotensin I appears to have no direct biological activity and exists solely as a precursor to angiotensin II.

Angiotensin II

Asp-Arg-Val-Tyr-Ile-His-Pro-Phe[clarification needed]

Angiotensin I is converted to angiotensin II (AII) through removal of two C-terminal residues by the enzyme

paracrine, and intracrine
hormone.

ACE is a target of

Na+/H+ exchanger in the proximal tubules of the kidney to stimulate Na+ reabsorption and H+ excretion which is coupled to bicarbonate reabsorption. This ultimately results in an increase in blood volume, pressure, and pH.[16] Hence, ACE inhibitors
are major anti-hypertensive drugs.

Other cleavage products of ACE, seven or nine amino acids long, are also known; they have differential affinity for

angiotensin II AT1 receptors
.

Angiotensin II is degraded to angiotensin III by angiotensinases located in red blood cells and the vascular beds of most tissues. Angiotensin II has a half-life in circulation of around 30 seconds,[17] whereas, in tissue, it may be as long as 15–30 minutes.

Angiotensin II results in increased

congestive heart failure.[15]

Angiotensin III

Asp | Arg-Val-Tyr-Ile-His-Pro-Phe[clarification needed]

Angiotensin III, along with angiotensin II, is considered an active peptide derived from angiotensinogen.[18]

Angiotensin III has 40% of the

pressor activity of angiotensin II, but 100% of the aldosterone-producing activity. Increases mean arterial pressure. It is a peptide that is formed by removing an amino acid from angiotensin II by glutamyl aminopeptidase A, which cleaves the N-terminal Asp residue.[19]

Activation of the AT2 receptor by angiotensin III triggers natriuresis, while AT2 activation via angiotensin II does not. This natriuretic response via angiotensin III occurs when the AT1 receptor is blocked.[20]

Angiotensin IV

Arg | Val-Tyr-Ile-His-Pro-Phe[clarification needed]

Angiotensin IV is a hexapeptide that, like angiotensin III, has some lesser activity. Angiotensin IV has a wide range of activities in the central nervous system.[21][22]

The exact identity of AT4 receptors has not been established. There is evidence that the AT4 receptor is insulin-regulated aminopeptidase (IRAP).[23] There is also evidence that angiotensin IV interacts with the HGF system through the c-Met receptor.[24][25]

Synthetic

blood brain barrier have been developed.[25]

The AT4 site may be involved in memory acquisition and recall, as well as blood flow regulation.[26] Angiotensin IV and its analogs may also benefit spatial memory tasks such as object recognition and avoidance (conditioned and passive avoidance).[27] Studies have also shown that the usual biological effects of angiotensin IV on the body are not affected by common AT2 receptor antagonists such as the hypertension medication Losartan.[27]

Effects

See also Renin–angiotensin system#Effects

Angiotensins II, III and IV have a number of effects throughout the body:

Adipic

Angiotensins "modulate fat mass expansion through upregulation of adipose tissue lipogenesis ... and downregulation of lipolysis."[28]

Cardiovascular

Angiotensins are potent direct

vasoconstrictors, constricting arteries and increasing blood pressure. This effect is achieved through activation of the GPCR AT1, which signals through a Gq protein to activate phospholipase C, and subsequently increase intracellular calcium.[29]

Angiotensin II has prothrombotic potential through adhesion and aggregation of

Neural

Angiotensin II increases

ACTH from the anterior pituitary.[32] Some evidence suggests that it acts on the organum vasculosum of the lamina terminalis (OVLT) as well.[35]

Adrenal

Angiotensin II acts on the adrenal cortex, causing it to release aldosterone, a hormone that causes the kidneys to retain sodium and lose potassium. Elevated plasma angiotensin II levels are responsible for the elevated aldosterone levels present during the luteal phase of the menstrual cycle.

Renal

Angiotensin II has a direct effect on the proximal tubules to increase Na+

glomerular filtration and renal blood flow depending on the setting. Increases in systemic blood pressure will maintain renal perfusion pressure; however, constriction of the afferent and efferent glomerular arterioles will tend to restrict renal blood flow. The effect on the efferent arteriolar resistance is, however, markedly greater, in part due to its smaller basal diameter; this tends to increase glomerular capillary hydrostatic pressure and maintain glomerular filtration rate. A number of other mechanisms can affect renal blood flow and GFR. High concentrations of Angiotensin II can constrict the glomerular mesangium, reducing the area for glomerular filtration. Angiotensin II is a sensitizer to tubuloglomerular feedback
, preventing an excessive rise in GFR. Angiotensin II causes the local release of prostaglandins, which, in turn, antagonize renal vasoconstriction. The net effect of these competing mechanisms on glomerular filtration will vary with the physiological and pharmacological environment.

Direct Renal effects of angiotensin II (not including aldosterone release)
Target Action Mechanism[36]
renal artery &
afferent arterioles
vasoconstriction (weaker)
VDCCs → Ca2+
influx
efferent arteriole vasoconstriction (stronger) (probably) activate
IP3 receptor in SR
→ ↑intracellular Ca2+
mesangial cells contraction → ↓filtration area
proximal tubule increased Na+ reabsorption
  • adjustment of
    Starling forces
    in peritubular capillaries to favour increased reabsorption
    • efferent and afferent arteriole contraction → decreased hydrostatic pressure in peritubular capillaries
    • efferent arteriole contraction → increased filtration fraction → increased colloid osmotic pressure in peritubular capillaries
  • increased sodium–hydrogen antiporter activity
tubuloglomerular feedback increased sensitivity increase in
afferent arteriole responsiveness to signals from macula densa
medullary blood flow reduction

See also

References

  1. PMID 11751697
    .
  2. ^ a b c GRCh38: Ensembl release 89: ENSG00000135744 - Ensembl, May 2017
  3. ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000031980 - Ensembl, May 2017
  4. ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  6. ^ "Angiotensin | Hormone Health Network". www.hormone.org. Retrieved 2019-12-02.
  7. ^
    PMID 26888118
    .
  8. ^ "AGT - Angiotensinogen precursor - Homo sapiens (Human) - AGT gene & protein". www.uniprot.org. Retrieved 2019-12-02.
  9. ^
    S2CID 29751589
    .
  10. .
  11. .
  12. .
  13. .
  14. .
  15. ^ .
  16. ^ Le T (2012). First Aid for the Basic Sciences. Organ Systems. McGraw-Hill. p. 625.
  17. PMID 29763087
    .
  18. .
  19. ^ "Angiotensin III". PubChem. NIH. Retrieved 9 May 2019.
  20. S2CID 37807540
    .
  21. .
  22. .
  23. .
  24. .
  25. ^ .
  26. .
  27. ^ .
  28. .
  29. .
  30. .
  31. .
  32. ^ .
  33. .
  34. .
  35. OCLC 1076268769.{{cite book}}: CS1 maint: location missing publisher (link
    )
  36. .

Further reading

External links