The angiotensin II type 2 receptor: an enigma with multiple variations

Since it was discovered ten years ago, the angiotensin II (ANG II) type 2 ( AT(2)) receptor has been an enigma. This receptor binds ANG II with a high affinity but is not responsible for mediating any of the classical physiolo gical actions of this peptide, all of which involve the ANG II type I (AT(1 )) receptor. Furthermore, the AT(2) receptor exhibits dramatic differences in biochemical and functional properties and in patterns of expression comp ared with the AT(1) receptor. During the past decade, much information has been gathered about the AT(2) receptor, and the steadily increasing number of publications indicates a growing interest in this new and independent ar ea of research. A number of studies suggest a role of AT(2) receptors in br ain, renal, and cardiovascular functions and in the processes of apoptosis and tissue regeneration. Despite these advances, nothing stands out as the major singular function of these receptors. The study of AT(2) receptors ha s reached a crossroads, and innovative approaches must be considered so tha t unifying mechanisms as to the function of these unique receptors can be p ut forward. In this review we will discuss the advances that have been made in understanding the biology of the AT(2) receptor. Furthermore, we will c onsider how these discoveries, along with newer experimental approaches, ma y eventually lead to the elusive physiological and pathophysiological funct ions of these receptors.