MOLECULAR-BIOLOGY OF ANGIOTENSIN RECEPTORS - TARGET FOR DRUG RESEARCH

Angiotensin II receptors: Angiotensin II is a key regulator of cardiovascular homeostasis. At least two distinct angiotensin II receptor subtypes are defined, on the basis of their differential pharmacological and biochemical properties, and designated as type 1 (AT(1)) and type 2 (AT(2)) receptors. AT(1) subtypes: Recent cloning has revealed that the AT(1) type belongs to a seven-transmembrane, G protein-coupled receptor superfamily. The AT(1) receptor comprises two isoforms, AT(1), and AT(1b), which are strikingly similar in amino acid structure, pharmacological specificity and signal transduction mechanism. To date, the evidence indicates that almost all of the known effects of angiotensin II in adult tissues are attributable to the AT(1) receptor. AT(2) subtype: Much less is known about the function of the AT(2) receptor, but its abundant expression in fetal tissues, immature brain, skin wounds, and atretic ovarian follicles suggest that it affects growth and development. The AT(2) receptor complementary (c)DNA has recently been cloned. It encodes a 363 amino acid protein with unique tissue distributions and developmental patterns. It is 34% identical in sequence to the AT(1) receptor, sharing a seven-transmembrane domain topology. Conclusions: Further research in defining the functions of the AT(1) and AT(2) receptor subtypes in cardiovascular regulation will provide new opportunities for new drug discovery and for the characterization of angiotensin II antagonists.