Renal proximal tubular AT(2) receptor: Signaling and transport

Previous studies have documented that the vasoactive agonist angiotensin II (AngII) directly affects proximal tubular sodium-bicarbonate reabsorption in a biphasic manner, whereby picomolar concentrations promote reabsorption and nanomolar concentrations have the converse effect. Although it is gene rally agreed that the AT(1) receptor subtype mediates AngII-induced sodium- bicarbonate reabsorption primarily through adenylate cyclase, the receptor subtype mediating natriuresis is less well defined. Using mouse proximal tu bular cells, this study documents AT(1)-dependent enhancement (candesartan- inhibitable) of bicarbonate reabsorption and AT(2)-induced (PD123319- and C GP42112A-inhibitable) decrement of bicarbonate absorption. The signaling me chanisms were examined in rabbit proximal tubule cells in culture. The AT(2 ) signaling involves G protein beta- and gamma-mediated phospholipase A(2) activation, arachidonic acid release, and downstream events linked to Shc/G rb(2)/Sos and p21(ras) rather than protein kinase C as reported previously for AngII receptors. These observations provide a novel mechanism for AngII -AT(2) receptor-mediated transport modulation.