Differential expression of Na+-Cl- cotransporter and Na+-K+-Cl- cotransporter 2 in the distal nephrons of euryhaline and seawater pufferfishes

Akira Kato, Takayuki Muro, Yuuri Kimura, Shanshan Li, Zinia Islam, Maho Ogoshi, Hiroyuki Doi, Shigehisa Hirose

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40 Citations (Scopus)


The process of NaCl reabsorption in the distal nephron allows freshwater fishes to excrete hypotonic urine and seawater fishes to excrete urine containing high concentrations of divalent ions; the relevant transporters, however, have not yet been identified. In the mammalian distal nephron, NaCl absorption is mediated by Na+-K+-Cl- cotransporter 2 (NKCC2, Slc12a1) in the thick ascending limb, Na +-Cl- cotransporter (NCC, Slc12a3) in the distal convoluted tubule, and epithelial sodium channel (ENaC) in the collecting duct. In this study, we compared the expression profiles of these proteins in the kidneys of euryhaline and seawater pufferfishes. Mining the fugu genome identified one NKCC2 gene and one NCC gene, but no ENaC gene. RT-PCR and in situ hybridization analyses demonstrated that NKCC2 was highly expressed in the distal tubules and NCC was highly expressed in the collecting ducts of euryhaline pufferfish (mefugu, Takifugu obscurus). On the other hand, the kidney of seawater pufferfish (torafugu, Takifugu rubripes), which lacked distal tubules, expressed very low levels of NCC, and, in the collecting ducts, high levels of NKCC2. Acclimation of mefugu to seawater resulted in a 2.7x decrease in NCC expression, whereas NKCC2 expression was not markedly affected. Additionally, internalization of NCC from the apical surface of the collecting ducts was observed. These results suggest that NaCl reabsorption in the distal nephron of the fish kidney is mediated by NCC and NKCC2 in freshwater and by NKCC2 in seawater.

Original languageEnglish
Pages (from-to)R284-R297
JournalAmerican Journal of Physiology - Regulatory Integrative and Comparative Physiology
Issue number2
Publication statusPublished - Feb 2011
Externally publishedYes


  • Collecting duct
  • Dilute urine
  • Distal tubule
  • Fish kidney
  • NCC
  • NKCC2

ASJC Scopus subject areas

  • Physiology
  • Physiology (medical)


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