The AT2 receptor: fact, fancy and fantasy.
The angiotensin AT2 receptor subtype was recently cloned and pharmacologically characterized but its function still remains elusive and controversial. It is a member of the G-protein coupled receptor superfamily with a minimal sequence homology with the AT1 receptor, responsible for the known effect of angiotensin II. The AT2 receptor displays a totally different signaling mechanisms from the AT1 receptor and involves various phosphatases. It is expressed at low density in adult tissues but up-regulated in pathological circumstances. Clearly, the AT2 receptor has antiproliferative properties and therefore opposes the growth promoting effect linked to the AT1 receptor stimulation. It is also reported that the AT2 receptor regulates ionic fluxes, affects differentiation and nerve regeneration, has anti-angiogenic and anti-fibrotic properties and stimulates apoptosis. However, the results, although suggestive, are sometimes equivocal. Obviously, the AT2 receptor plays a role in the pathogenesis and remodeling of cardiovascular and renal diseases. A more extensive knowledge of the AT2 receptor could therefore contribute to the understanding of the clincial beneficial effects of the AT1 receptor antagonists.
de Gasparo
M
M
Novartis Pharma AG, Basel, Switzerland. marc.de_gasparo@pharma.novartis.com
Siragy
H M
HM
D000818:Animals; D017209:Apoptosis; D002118:Calcium / Q000378:metabolism; D002454:Cell Differentiation; D002455:Cell Division; D002490:Central Nervous System / Q000378:metabolism*; D003094:Collagen / Q000378:metabolism; D005109:Extracellular Matrix / Q000378:metabolism*; D005260:Female; D006801:Humans; D008297:Male; D009215:Myometrium / Q000378:metabolism; D018919:Neovascularization, Physiologic / Q000502:physiology*; D009474:Neurons / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D012098:Reproduction / Q000502:physiology*; D015854:Up-Regulation
D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D003094:Collagen; D011188:Potassium; D002118:Calcium