Angiotensin IV AT4-receptor system in the rat kidney

Angiotensin IV, {[des-Asp(1),Arg(2)]ANG II or ANG-(3-8)}, has been shown to preferentially bind to a novel angiotensin binding site (AT(4) receptor). The cellular location and function of this receptor in the rat kidney is unknown, Autoradiography localized AT(4) receptors to the cell body and apical membrane of convoluted and straight proximal tubules in the cortex and outer stripe of the outer medulla, ANG IV (0.1 pM-1 mu M) elicited a concentration-dependent decrease in transcellular Na(+) transport (as measured by proximal tubule O(2) consumption rates) in fresh suspensions of control or nystatin-stimulated (bypasses rate-limiting step of apical Na(+) entry) rat proximal tubules. The inhibitory effect of 1 pM ANG IV was unaltered by either 1 mu M losartan (AT(1)-receptor antagonist) or 1 mu M PD-123319 (AT(2)-receptor antagonist) and yet was abolished by 1 mu M divalinal-ANG IV (AT(4)-receptor antagonist) or ouabain pretreatment. These results demonstrate that the kidney AT(4)-receptor system is localized to the proximal tubule anti suggests that one potential biological role Of this system is is the regulation of Na(+) transport by inhibiting a ouabain-sensitive component of Na(+)-K(+)-adenosinetriphosphatase activity in the rat.