Angiotensin II receptor

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The blood pressure-increasing hormone angiotensin II (AT) unfolds its effect at the target site via the angiotensin II receptor . Since the 1980s, however, several types of receptors have been differentiated by different, non- peptide inhibitors, of which the two best investigated are called angiotensin AT 1 receptor (AT 1 R) and angiotensin AT 2 receptor (AT 2 R). Both types of receptors belong to the family of receptors with seven transmembrane domains , but differ significantly from one another both in structure and in distribution in the body and thus in function.

AT 1 receptor

The AT 1 receptor is a G-protein-coupled receptor that exists in two isoforms. The activated receptor binds to the proteins G q / 11 and G i / o , whereby the phospholipase C is activated and the concentration of calcium Ca 2+ in the cytosol is increased. This then mediates effects such as vasoconstriction and stimulation of protein kinase C at the molecular level . In addition to the vascular system and heart, the AT 1 receptor can also be detected in the brain , kidneys and adrenal glands as well as in the liver and intestines .

By activating the AT 1 receptor, the effects, such as an increase in blood pressure , which were first described in the 19th century, are mediated. This happens on the one hand by increasing the vascular resistance through vasoconstriction , on the other hand by increasing cardiac contractility. In the kidney, the filtration rate is kept as constant as possible by contracting the blood vessels leading away. In the adrenal gland, angiotensin II stimulates the release of aldosterone and adrenaline via this type of receptor , and a release of vasopressin in the pituitary gland . The feeling of thirst is also attributed to acute stimulation of AT 1 receptors in the hypothalamus .

In addition, the chronic effect via this type of receptor is also responsible for the changes in the blood vessels that are important in the development of the long-term damage caused by high blood pressure, such as increased cell growth with fibrosis and maintenance of the inflammatory reaction . In order to prevent these negative consequences in diseases, special inhibitors of this receptor have been developed, the so-called AT 1 antagonists .

AT 2 receptor

The action via the AT 2 receptor is fundamentally different and in some cases even opposite to that which angiotensin II exerts via the AT 1 receptor. Physiological effects consist of an inhibition of the growth of endothelial cells in coronary vessels .

In addition, an experimental stimulation of the AT 2 receptor by the selective agonist CGP 42112A leads to an increased release of nitric oxide (NO) in the mucous membranes, which causes an improved blood flow. In blood vessels, stimulation of the AT 2 receptor usually leads to a reduction in blood pressure, but sometimes only with a blockade of the AT 1 receptor.

In the case of many of the experimentally found effects via the AT 2 receptor, it has not yet been clarified to what extent they play a role in the development of diseases or their prevention.

Individual evidence

  1. ↑ S. Whitebread, M. Mele, B. Kamber, M. de Gasparo: Preliminary biochemical characterization of two angiotensin II receptor subtypes. In: Biochem. Biophys. Res. Commun. 163 (1), 1989, pp. 284-291.
  2. ↑ RC Speth, KH Kim: Discrimination of two angiotensin II receptor subtypes with a selective agonist analogue of angiotensin II, p-aminophenylalanine6 angiotensin II. In: Biochem. Biophys. Res. Commun. 169 (3), 1990, pp. 997-1006.
  3. ↑ S. Higuchi, H. Ohtsu, H. Suzuki, H. Shirai, GD Frank, S. Eguchi: Angiotensin II signal transduction through the AT1 receptor: novel insights into mechanisms and pathophysiology. In: Clinical Science. 112, 8, Apr 2007, pp. 417-428.
  4. ↑ Gunter Wolf, Rolf AK Stahl: Angiotensin II effects on the kidneys: more than a vasoconstrictor. In: Deutsches Ärzteblatt. 93, 31-32, Aug 5, 1996, pp. A-2039-A2042.
  5. ^ ER Porrello, LMD Delbridge, WG Thomas: The angiotensin II type 2 (AT2) receptor: an enigmatic seven transmembrane receptor. In: Front. Biosci. 14, 2009, pp. 958-972.
  6. ↑ Sara Ewert, Mats Laesser, Bernalt Johansson, Mathias Holm, Anders Aneman, Lars Fandriks: The angiotensin II receptor type 2 agonist CGP 42112A stimulates NO production in the porcine jejunal mucosa. In: BMC Pharmacology. 3, p. 2, doi: 10.1186 / 1471-2210-3-2 . PMC 153509 (free full text).
  7. ↑ C. Dimitropoulou, RE White, L. Fuchs et al .: Angiotensin II relaxes microvessels via the AT (2) receptor and Ca (2 +) - activated K (+) (BK (Ca)) channels. In: Hypertension 37 (2), 2001, pp. 301-307.

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