ANGIOTENSIN-II RECEPTORS - CLASSIFICATION, STRUCTURE AND SIGNAL-TRANSDUCTION

Angiotensin II (AngII), a circulating vasoactive pep tide, interacts w ith specific membrane-bound receptors on the target tissues (vessels, kidneys and adrenal gland). Using new pharmacological tools and molecu lar cloning, these receptors have been classified in two types, called AT(1) et AT(2), whereas two subtypes, called AT(1A) et AT(1B), have b een identified for the rodent AT(1) receptors, but not in humans. All these receptors present a seven hydrophobic transmembrane domain struc ture, which is classical for G protein coupled receptors. The interspe cies molecular homology of these AngII receptors is high (>90 per cent identity) within the same type of receptor, but is rather low (approx imate to 35 per cent identity) between the two types of receptors. The AT(1) receptors are responsible for most of the AngII physiological a ctions and are coupled to a Gq protein, which activates a phospholipas e C producing second messengers which activate protein kinases C and m obilize calcium intracellular stores. More recently, a strong interact ion of this receptor has been demonstrated with the signalling pathway s of the tyrosine kinases. The molecular mechanisms and the physiologi cal importance of these interactions remain to be elucidated. The intr acellular signalling (Gi coupling and tyrosine phosphatase activation) and the physiological actions (cellular differentiation, apoptosis) o f the AT(2) receptors are more controversial.