Angiotensin receptors.
BACKGROUND
The octapeptide angiotensin II, the potent effector molecule of the renin-angiotensin system, has been implicated in the pathology of hypertension, in cardiovascular diseases like cardiac left ventricular hypertrophy and in structural alterations of the heart such as post-infarct remodelling.
The development of highly selective angiotensin II receptor ligands allowed the identification of angiotensin II receptor subtypes, designated AT1, AT2, AT3 and AT4. Most of the known effects of angiotensin II can be attributed to the AT1 receptor (e.g. vasoconstriction, aldosterone and vasopressin release and proliferative effects on vascular smooth muscle and other cells). The AT1 receptor is coupled to G-proteins and engages classical intracellular second messenger systems, for example activation of phospholipase C or inhibition of adenylate cyclase. In contrast, the function and the signal transduction pathways of the AT2 receptor, which exhibits only a 32-34% homology to the AT1 receptor, are so far not fully understood. Coupling of the AT2 receptor to phosphatases and inhibitory actions on AT1 receptor- and growth factor-mediated proliferation in endothelial and other cells as well as induction of neuronal outgrowth in PC12w cells have been demonstrated. Due to its wide distribution in fetal tissues including the central nervous system and its transient reappearance in the adult organism under pathological conditions (for instance after myocardial infarction) the AT2 receptor has been associated with cell differentiation and regeneration.
The application of orally active AT1 receptor antagonists as antihypertensive drugs has, compared to angiotensin converting enzyme inhibitors, the potential advantage of a more specific renin-angiotensin system inhibition. It is conceivable that the AT2 receptor, left unopposed by AT1 receptor antagonists, contributes to some of the actions of these drugs.
Unger
T
T
Department of Pharmacology, Christian-Albrechts University of Kiel, Germany.
Chung
O
O
Csikos
T
T
Culman
J
J
Gallinat
S
S
Gohlke
P
P
Höhle
S
S
Meffert
S
S
Stoll
M
M
Stroth
U
U
Zhu
Y Z
YZ
D000818:Animals; D017209:Apoptosis / Q000502:physiology; D001808:Blood Vessels / Q000293:injuries; D001921:Brain / Q000502:physiology; D004730:Endothelium, Vascular / Q000473:pathology; D006801:Humans; D011945:Receptors, Angiotensin / Q000502:physiology*; D015398:Signal Transduction; D017539:Tunica Intima / Q000254:growth & development; D014661:Vasoconstriction / Q000502:physiology
D011945:Receptors, Angiotensin