Molecular biology of angiotensin receptors: target for drug research?

UNLABELLED: 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 (AT1) and type 2 (AT2) receptors. AT1 subtypes: Recent cloning has revealed that the AT1 type belongs to a seven-transmembrane, G protein-coupled receptor superfamily. The AT1 receptor comprises two isoforms, AT1a and AT1b, 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 AT1 receptor. AT2 subtype: Much less is known about the function of the AT2 receptor, but its abundant expression in fetal tissues, immature brain, skin wounds, and atretic ovarian follicles suggest that it affects growth and development. The AT2 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 AT1 receptor, sharing a seven-transmembrane domain topology. CONCLUSIONS: Further research in defining the functions of the AT1 and AT2 receptor subtypes in cardiovascular regulation will provide new opportunities for new drug discovery and for the characterization of angiotensin II antagonists.

Duke Scholars

Author Victor J. Dzau Medicine, Cardiology