H-K-ATPase in distal renal tubular acidosis: urinary tract obstruction, lithium, and amiloride

• Published in: American journal of physiology. Renal physiology Vol. 265; no. 6 Pt 2; pp. F875 - F880
• Main Authors: Eiam-Ong, S, Dafnis, E, Spohn, M, Kurtzman, N A, Sabatini, S
• Format: Journal Article
• Language: English
• Published: United States 01.12.1993
• Subjects: Acidosis - metabolism; Aldosterone - blood; Amiloride - pharmacology; Animals; H(+)-K(+)-Exchanging ATPase - metabolism; Kidney Tubules, Collecting - enzymology; Kidney Tubules, Distal - metabolism; Lithium - pharmacology; Male; Rats; Rats, Sprague-Dawley; Ureteral Obstruction - metabolism
• ISSN: 0002-9513; 1931-857X; 1522-1466
• DOI: 10.1152/ajprenal.1993.265.6.F875

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.