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Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, College of Veterinary Medicine, Washington State University, Pullman, Washington 99164
Angiotensin IV,
{[des-Asp1,Arg2]ANG
II or ANG-(3
8)}, has been shown to preferentially bind to a novel
angiotensin binding site (AT4
receptor). The cellular location and function of this receptor in the
rat kidney is unknown. Autoradiography localized
AT4 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 µM)
elicited a concentration-dependent decrease in transcellular
Na+ transport (as measured by
proximal tubule O2 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 µM losartan
(AT1-receptor antagonist) or 1 µM PD-123319 (AT2-receptor
antagonist) and yet was abolished by 1 µM divalinal-ANG IV
(AT4-receptor antagonist) or
ouabain pretreatment. These results demonstrate that the kidney
AT4-receptor system is localized
to the proximal tubule and suggests that one potential biological role
of this system is in the regulation of
Na+ transport by inhibiting a
ouabain-sensitive component of
Na+-K+-adenosinetriphosphatase
activity in the rat.
oxygen consumption; sodium transport; proximal tubule; autoradiography
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