skip to main content

Title: Inhibition of renal Na{sup +}/H{sup +} exchange in cadmium-intoxicated rats

Chronic exposure to cadmium (Cd) results in bicarbonaturia, leading to metabolic acidosis. To elucidate the mechanism(s) by which renal bicarbonate reabsorption is inhibited, we investigated changes in renal transporters and enzymes associated with bicarbonate reabsorption in Cd-intoxicated rats. Cd intoxication was induced by subcutaneous injections of CdCl{sub 2} (2 mg Cd/kg per day) for 3 weeks. Cd intoxication resulted in a significant reduction in V{sub max} of Na{sup +}/H{sup +} antiport with no changes in K{sub Na} in the renal cortical brush-border membrane vesicles (BBMV). Western blotting of BBM proteins and indirect immunohistochemistry in renal tissue sections, using an antibody against Na{sup +}/H{sup +} exchange-3 (NHE3), showed a diminished expression of NHE3 protein in the BBM. Reverse transcription-polymerase chain reaction (RT-PCR) analysis revealed that NHE3 mRNA expression was reduced in the renal cortex. The activity of carbonic anhydrase IV (CA IV) in BBM was not changed. The protein abundance of Na{sup +}-HCO{sub 3}{sup -} cotransporter-1 (NBC1) in whole kidney membrane fractions was slightly attenuated, whereas that of the Na{sup +}-K{sup +}-ATPase {alpha}-subunit was markedly elevated in Cd-intoxicated animals. These results indicate that Cd intoxication impairs NHE3 expression in the proximal tubule, thereby reducing the capacity for bicarbonate reabsorption, leading tomore » bicarbonaturia in an intact animal.« less
Authors:
 [1] ;  [1] ;  [1] ;  [1] ;  [2]
  1. Department of Physiology, Kosin University College of Medicine, Busan 602-702 (Korea, Republic of)
  2. Department of Physiology, Kosin University College of Medicine, Busan 602-702 (Korea, Republic of). E-mail: yspark@ns.kosinmed.or.kr
Publication Date:
OSTI Identifier:
20721780
Resource Type:
Journal Article
Resource Relation:
Journal Name: Toxicology and Applied Pharmacology; Journal Volume: 204; Journal Issue: 1; Other Information: DOI: 10.1016/j.taap.2004.08.021; PII: S0041-008X(04)00410-7; Copyright (c) 2004 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; ACID CARBONATES; ANTIBODIES; CADMIUM CHLORIDES; CARBONIC ANHYDRASE; CHRONIC EXPOSURE; INHIBITION; POLYMERASE CHAIN REACTION; POTASSIUM IONS; RATS; SODIUM IONS; SUBCUTANEOUS INJECTION; TRANSCRIPTION; TUBULES