Angiotensin receptors: Molecular biology and signalling

1. The active peptide hormone angiotensin II (AngII) is formed from its pro hormone angiotensinogen by way of inactive angiotensin I. The highly specif ic protease, renin, responsible for the initiation of this system was elusi ve and considered unstable. We isolated it in a pure and stable form from t he kidney of the pig, human, rat, and land submandibular glands of the mous e. It was shown that there is only one type of renin nifh highly Stringent substrate specificity, except certain strains of the mouse which have two g ene products. 2. The well-known diversity of action of AngII can be attributed to the pre sence of more than two subtypes, AT(1) and AT(2), as well as multiple signa lling pathways for both of them, 3. The first subtype AT(1) was shown to mediate most of the traditionally r ecognized AngII functions such as vasoconstriction, electrolyte homeostasis etc. 4. Although the identification of the signalling modes of the second subtyp e AT(2) still remains elusive, we and others have shown evidence that its a ction is generally antagonistic to that of AT(1).AT(2) inhibits AT(1) (grow th factor-stimulated cell growth), AT(2) attenuates the vasoconstriction in duced by AT(1), Since AT(2) seems to mediate nitric oxide formation in the renal cells, it may initiate a natriuretic pathway in contrast to the sodiu m-retaining action of AT(1)-mediated AngII action. 5. Newer mechanisms and functions of these and other receptors will be clar ified by the combination of molecular, cellular and integrated physiologica l studies.