Angiotensin receptors: molecular biology and signalling

1. The active peptide hormone angiotensin II (AngII) is formed from its prohormone angiotensinogen by way of inactive angiotensin I. The highly specific protease, renin, responsible for the initiation of this system was elusive and considered unstable. We isolated it in a pure and stable form from the kidney of the pig, human, rat, and land submandibular glands of the mouse. It was shown that there is only one type of renin with highly stringent substrate specificity, except certain strains of the mouse which have two gene products. 2. The well-known diversity of action of AngII can be attributed to the presence of more than two subtypes, AT1 and AT2, as well as multiple signalling pathways for both of them. 3. The first subtype AT1 was shown to mediate most of the traditionally recognized AngII functions such as vasoconstriction, electrolyte homeostasis etc. 4. Although the identification of the signalling modes of the second subtype AT2 still remains elusive, we and others have shown evidence that its action is generally antagonistic to that of AT1. AT2 inhibits AT1 (growth factor-stimulated cell growth), AT2 attenuates the vasoconstriction induced by AT1. Since AT2 seems to mediate nitric oxide formation in the renal cells, it may initiate a natriuretic pathway in contrast to the sodium-retaining action of AT1-mediated AngII action. 5. Newer mechanisms and functions of these and other receptors will be clarified by the combination of molecular, cellular and integrated physiological studies.