ANGIOTENSIN-IV AT(4)-RECEPTOR SYSTEM IN THE RAT-KIDNEY

Angiotensin IV, {[des-Asp(1),Arg(2)]ANG II or ANG-(3-8)}, has been sho wn to preferentially bind to a novel angiotensin binding site (AT(4) r eceptor). The cellular location and function of this receptor in the r at kidney is unknown, Autoradiography localized AT(4) receptors to the cell body and apical membrane of convoluted and straight proximal tub ules in the cortex and outer stripe of the outer medulla, ANG IV (0.1 pM-1 mu M) elicited a concentration-dependent decrease in transcellula r 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 inhibito ry 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 anta gonist) or ouabain pretreatment. These results demonstrate that the ki dney AT(4)-receptor system is localized to the proximal tubule anti su ggests that one potential biological role Of this system is is the reg ulation of Na+ transport by inhibiting a ouabain-sensitive component o f Na+-K+-adenosinetriphosphatase activity in the rat.