Angiotensin II
| Angiotensin II | ||
|---|---|---|
|
||
| Dome model according to PDB 1N9V | ||
| Properties of human protein | ||
| Mass / length primary structure | 8 amino acids | |
| Precursor | Angiotensinogen | |
| Identifier | ||
| Gene names | AGT ; ANHU; SERPINA8 | |
| External IDs | ||
| Drug information | ||
| ATC code | C01 CX06 | |
Angiotensin II is a to the tissue hormones scoring peptide hormone consisting of eight amino acids ( octapeptide ). It takes the key position in the for the maintenance of blood pressure and water balance responsible renin-angiotensin system , a (RAAS).
biochemistry
structure
The primary structure of angiotensin II consists of eight amino acids (H 2 N-Asp-Arg-Val-Tyr-Ile-His-Pro-Phe-COOH) with a molecular mass of 1046.19 Da .
biosynthesis
Angiotensin II is enzymatically split from the decapeptide angiotensin I in the organism by the angiotensin converting enzyme (angiotensin converting enzyme, ACE). The angiotensin converting enzyme is the point of attack of the ACE inhibitors . Angiotensin I results from the enzymatic cleavage of angiotensinogen by renin . The primary stimulus for the release of renin (and ultimately also the formation of angiotensin II) is a reduced blood pressure in the kidney.
Mechanism of action
The angiotensin II formed interacts with angiotensin II receptors (AT receptors). By activating the AT 1 receptor , a contraction can primarily take place in blood vessels . In the kidney , the glomerular filtration rate is kept as constant as possible by constricting the efferent blood vessels . In the adrenal gland , angiotensin II stimulates the release of aldosterone and adrenaline, and in the pituitary gland it stimulates the release of vasopressin . The feeling of thirst is also attributed to acute stimulation of AT 1 receptors in the hypothalamus . Chronic stimulation of the AT 1 receptor, on the other hand, leads to a stimulation of mitogenic effects and thus, for example, to hypertrophy of the heart . Acute and chronic effects of angiotensin II on the AT 1 receptor can be suppressed indirectly by ACE inhibitors and directly by AT 1 receptor antagonists (sartans) or saralasin .
Angiotensin II also shows a high affinity for AT 2 receptors . The importance of these receptors in the effects mediated by angiotensin II is, however, controversial. Animal experiments on mice indicated that the effect on AT 2 receptors in the sense of counteracting this has a dampening effect on the effects on AT 1 receptors.
Angiotensinamide , a derivative of angiotensin II, is a cardio-stimulating and blood pressure-increasing drug.
Dismantling
Angiotensin II is broken down into inactive products by aminopeptidases in a multi-stage process. Any intermediate products such as angiotensin III and angiotensin IV can, however, still have biological activity. Angiotensin III binds to the AT 1 receptor with moderate potency , while angiotensin IV is a ligand to the as yet little researched AT 4 receptor.
An alternative pathway for cleavage of angiotensin II using the angiotensin-converting enzyme of type 2 was only recently discovered.
history
Angiotensin, originally called angiotonin or hypertensin, was first described in 1940 by IH Page. He found that the angiotensinogen produced in the liver is a substrate for the kidney-derived enzyme renin. As a result of an enzymatic conversion, a substance was found that leads to vasoconstriction and an increase in blood pressure . But it took more than a decade before Leonard T. Skeggs could show that angiotensin is a mixture of at least two different substances: the largely inactive angiotensin I and the vascular-contracting angiotensin II.
literature
- Walmor C. DeMello, Edward D. Frohlich: Renin angiotensin system and cardiovascular disease . Humana Press, New York 2009, ISBN 1-60761-185-6 .
- EM Abdel-Rahman, Th. Unger, Bernward A. Schölkens: Angiotensin Vol. 2 . Springer, Berlin / New York 2004, ISBN 3-540-40641-7 .
Individual evidence
- ↑ UniProt P01019
- ^ JP (John Parry) Griffin: The textbook of pharmaceutical medicine . Wiley-Blackwell, Chichester (West Sussex) / Hoboken NJ 2009, ISBN 1-4051-8035-8 , pp. 37 .
- ^ IH Page, OM Helmer: A Crystalline Pressor Substance (Angiotonin) Resulting from the Reaction Between Renin and Renin-Activator . In: J. Med.. . 71, No. 1, January 1940, pp. 29-42. PMID 19870942 . PMC 2134997 (free full text).
- ^ LT Skeggs, WH Marsh, JR Kahn, NP Shumway: The existence of two forms of hypertensin . In: J. Med.. . 99, No. 3, March 1954, pp. 275-82. PMID 13130799 . PMC 2136205 (free full text).