Angiotensin II regulates H(+)-ATPase activity in rat cortical collecting duct.
Angiotensin II (ANG II) plays an important role in the regulation of solute transport in the kidney, and its effect on proximal tubule sodium and fluid transport has been studied extensively. Although there is evidence that ANG II receptors are present also in the distal nephron and collecting duct, little is known about the physiological role of ANG II in these segments of the renal tubule. Preliminary studies in our laboratory suggest that ANG II may have both structural and functional effects on intercalated cells in the cortical collecting duct (CCD). Therefore, the present study examines the effect of ANG II on H(+)-adenosinetriphosphatase (H(+)-ATPase) and H(+)-K(+)-ATPase activity in individual CCD segments microdissected from collagenase-treated rat kidneys. The H(+)-ATPase was measured as bafilomycin-sensitive ATPase activity, and H(+)-K(+)-ATPase was measured as Sch-28080-sensitive ATPase activity, by a fluorometric microassay. Preincubation of CCD segments with ANG II, 10(-10)-10(-5) M, caused a dose-dependent decrease in H(+)-ATPase activity with maximum inhibition at 10(-8) M of ANG II. The inhibitory effect of ANG II was abolished when tubules were incubated with ANG II in the presence of 10(-6) M losartan, indicating that the inhibition was mediated via specific AT1 receptors. The AT2-receptor antagonist, PD-123319, had no effect on the ANG II-mediated inhibition of H(+)-ATPase activity. Preincubation of CCD segments with 10(-10) or 10(-7) M ANG II had no effect on H(+)-K(+)-ATPase activity.(ABSTRACT TRUNCATED AT 250 WORDS)
Tojo
A
A
Division of Nephrology, Hypertension, and Transplantation, College of Medicine, University of Florida, Gainesville 32610.
Tisher
C C
CC
Madsen
K M
KM
D000244:Adenosine Diphosphate / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology; D017364:Collagenases / Q000494:pharmacology; D005033:Ethylmaleimide / Q000494:pharmacology; D005260:Female; D017506:H(+)-K(+)-Exchanging ATPase / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D007672:Kidney Cortex / Q000201:enzymology*; D007685:Kidney Tubules, Collecting / Q000201:enzymology*; D019808:Losartan; D018942:Macrolides; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors* / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D000900:Anti-Bacterial Agents; D001713:Biphenyl Compounds; D007093:Imidazoles; D018942:Macrolides; D011725:Pyridines; D013777:Tetrazoles; D000804:Angiotensin II; C073402:PD 123319; D000244:Adenosine Diphosphate; D017364:Collagenases; D017506:H(+)-K(+)-Exchanging ATPase; D006180:Proton-Translocating ATPases; D019808:Losartan; D005033:Ethylmaleimide