2, Agtr1 and Agtr2, respectively. Of the two receptors, Agtr1 which is expressed in most tissues and which in rodents is represented by two genes that are 95% identical in their amino acid sequences, is the better understood system. The Agtr1 mediated pathway is involved in vasoconstriction, proliferation, hormone release and fluid homeostasis. Activated Agtr1 couples to members of the Galphaq family of heterotrimeric G proteins whose signal transduction leads to activation of phopholipase C followed by activation of protein kinase C signaling pathway and the events downstream of it. In response to AgtII, Agtr1 can also mediate G protein independent signaling. In addition, Agtr1 may be active in the absence of ligand binding. The powerful but potentially harmful effects elicited by Agtr1 are counterbalanced by the Agtr2 mediated signaling. This pathway promotes vasodilation, NO release and growth inhibition. Agtr2, initially believed not to engage heterotrimeric G proteins was later shown to couple to members of the Galphai family. Agtr2 activates several protein phosphatases in a G protein dependent and independent manner resulting in inactivation of MAPK cascades thus conducive to antiproliferative effects. Agtr2 also prompts release of nitric oxide (NO) and increase in intracellular cGMP levels in a manner that is both dependent and independent of bradykinin receptor 2 (B2) and leading to vasodilator effects. Like in the case of Agtr1, Agtr2 mediated signaling can be G protein as well as ligand independent. However, the molecular mechanisms of Agtr2 mediated signaling are not well understood and the currently available information, at times is thought of as being controversial. Agtr1 and Agtr2 can form homodimers as well as heterodimers with other GPCRs and with one another. Deregulation of AgtII signaling has been implicated in cardiovascular and renal disorders.

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