H-K-ATPase in distal renal tubular acidosis: urinary tract obstruction, lithium, and amiloride.
In previous studies we suggested that urinary tract obstruction and chronic administration of lithium or amiloride were models of "voltage-dependent" distal renal tubular acidosis (DRTA). Subsequently, differences among these three models suggested that the pathogenesis was far more complex than we originally proposed. A recent study showed that H-adenosinetriphosphatase (H-ATPase) activity was decreased in all three experimental models. In the current experiments we examined the effect of 24-h unilateral ureteral obstruction (UUO) and chronic administration of amiloride and lithium on collecting tubule H-K-ATPase, the other renal H-ATPase enzyme. In the obstructed kidney, cortical collecting tubule (CCT) H-K-ATPase activity was enhanced by 73 +/- 10.0%, whereas the enzyme activity in medullary collecting tubule (MCT) was decreased by 67 +/- 5.4%. In the normal contralateral kidney, activities of H-ATPase, H-K-ATPase, and Na-K-ATPase were increased by approximately 30% in both CCT and MCT. Following amiloride (3 mg.kg-1.day-1 x 3 days ip), rats had normal acid-base status, slight hyperkalemia, and markedly elevated plasma aldosterone levels. Both CCT and MCT H-K-ATPase activities in amiloride-treated rats were unchanged. After LiCl (4 meq.kg-1.day-1 x 3 days ip), rats developed mild metabolic acidosis and had normokalemia and normal aldosterone status. CCT H-K-ATPase activity in lithium-treated rats was decreased by 64 +/- 8.8%, whereas the enzyme activity in MCT remained unchanged. Lithium in vitro (30 meq/l) inhibited CCT, but not MCT, H-K-ATPase activity, whereas amiloride had no effect on the enzyme activity. (ABSTRACT TRUNCATED AT 250 WORDS)
Eiam-Ong
S
S
Department of Physiology, Texas Tech University Health Sciences Center, Lubbock 79430.
Dafnis
E
E
Spohn
M
M
Kurtzman
N A
NA
Sabatini
S
S
D000138:Acidosis / Q000378:metabolism*; D000450:Aldosterone / Q000097:blood; D000584:Amiloride / Q000494:pharmacology*; D000818:Animals; D017506:H(+)-K(+)-Exchanging ATPase / Q000378:metabolism*; D007685:Kidney Tubules, Collecting / Q000201:enzymology; D007686:Kidney Tubules, Distal / Q000378:metabolism*; D008094:Lithium / Q000494:pharmacology*; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D014517:Ureteral Obstruction / Q000378:metabolism*
D000450:Aldosterone; D000584:Amiloride; D008094:Lithium; D017506:H(+)-K(+)-Exchanging ATPase