Inhibition of renal Na+/H+ exchange in cadmium-intoxicated rats

Do Whan Ahn, Jin Chung, Jee Yeun Kim, Kyoung Ryong Kim, Yang Saeng Park

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

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 CdCl2 (2 mg Cd/kg per day) for 3 weeks. Cd intoxication resulted in a significant reduction in Vmax of Na+/H+ antiport with no changes in KNa 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+/H+ 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 +-HCO3 - cotransporter-1 (NBC1) in whole kidney membrane fractions was slightly attenuated, whereas that of the Na +-K+-ATPase α-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 to bicarbonaturia in an intact animal.

Original languageEnglish (US)
Pages (from-to)91-98
Number of pages8
JournalToxicology and Applied Pharmacology
Volume204
Issue number1
DOIs
StatePublished - Apr 1 2005
Externally publishedYes

Fingerprint

Cadmium
Rats
Kidney
Bicarbonates
Carbonic Anhydrase IV
Animals
Membranes
Cadmium Chloride
Proteins
Polymerase chain reaction
Ion Transport
Brushes
Subcutaneous Injections
Transcription
Microvilli
Acidosis
Reverse Transcription
Adenosine Triphosphatases
Western Blotting
Immunohistochemistry

Keywords

  • Cadmium
  • Carbonic anhydrase
  • Kidney
  • Na /HCO cotransporter
  • Na/H exchanger

ASJC Scopus subject areas

  • Pharmacology
  • Toxicology

Cite this

Inhibition of renal Na+/H+ exchange in cadmium-intoxicated rats. / Ahn, Do Whan; Chung, Jin; Kim, Jee Yeun; Kim, Kyoung Ryong; Park, Yang Saeng.

In: Toxicology and Applied Pharmacology, Vol. 204, No. 1, 01.04.2005, p. 91-98.

Research output: Contribution to journalArticle

Ahn, Do Whan ; Chung, Jin ; Kim, Jee Yeun ; Kim, Kyoung Ryong ; Park, Yang Saeng. / Inhibition of renal Na+/H+ exchange in cadmium-intoxicated rats. In: Toxicology and Applied Pharmacology. 2005 ; Vol. 204, No. 1. pp. 91-98.
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