ANGIOTENSIN-II RECEPTOR SUBTYPES - THEIR DISTRIBUTION, SIGNALING PATHWAYS, AND PHYSIOLOGICAL FUNCTIONS

Angiotensin II (Ang II) exhibits a variety of physiological actions, r elated mainly to the regulation of blood pressure and fluid osmolarity . Recent identification of the multiple types of the Ang II receptors raises the possibility that Ang II has other unknown functions. The An g II type 1 receptor (AT(1)) mediates most of the known physiological functions of Ang II, whereas the type 2 receptor (AT(2))-mediated func tions remain unclear. AT(2) is particularly interesting because it is expressed abundantly in fetal tissues and in cells undergoing apoptosi s. AT(1) and AT(2) exhibit unique signaling pathways among the superfa mily of seven membrane-spanning receptors: i.e. the coupling of AT(1) to the Janus kinase-signal transducers and activators of transcription pathway and the coupling of AT(2) to phosphatase activation. Also, th e two subtypes induce several opposite intracellular events. AT(1) med iates activation of Ca2+ channels and inhibition of K+ channels, where as AT(2) induces inhibition of Ca2+ channels and activation of K+ chan nels. Therefore, it is of great importance to compare the two receptor subtypes with respect to their distribution, signaling pathways, and physiological functions.