Effect of collecting duct-specific deletion of both Rh B glycoprotein (Rhbg) and Rh C glycoprotein (Rhcg) on renal response to metabolic acidosis

Hyun Wook Lee, Jill W. Verlander, Mary E. Handlogten, Ki Hwan Han, I. David Weiner

Research output: Contribution to journalArticlepeer-review

29 Scopus citations

Abstract

The Rhesus (Rh) glycoproteins, Rh B and Rh C Glycoprotein (Rhbg and Rhcg, respectively), are ammonia-specific transporters expressed in renal distal nephron and collecting duct sites that are necessary for normal rates of ammonia excretion. The purpose of the current studies was to determine the effect of their combined deletion from the renal collecting duct (CD-Rhbg/Rhcg-KO) on basal and acidosis-stimulated acid-base homeostasis. Under basal conditions, urine pH and ammonia excretion and serum HCO-3 were similar in control (C) and CD-Rhbg/Rhcg-KO mice. After acid-loading for 7 days, CD-Rhbg/ Rhcg-KO mice developed significantly more severe metabolic acidosis than did C mice. Acid loading increased ammonia excretion, but ammonia excretion increased more slowly in CD-Rhbg/Rhcg-KO and it was significantly less than in C mice on days 1-5. Urine pH was significantly more acidic in CD-Rhbg/Rhcg-KO mice on days 1, 3, and 5 of acid loading. Metabolic acidosis increased phosphenolpyru-vate carboxykinase (PEPCK) and Na+/H+ exchanger NHE-3 and decreased glutamine synthetase (GS) expression in both genotypes, and these changes were significantly greater in CD-Rhbg/Rhcg-KO than in C mice. We conclude that 1) Rhbg and Rhcg are critically important in the renal response to metabolic acidosis; 2) the significantly greater changes in PEPCK, NHE-3, and GS expression in acid-loaded CD-Rhbg/Rhcg-KO compared with acid-loaded C mice cause the role of Rhbg and Rhcg to be underestimated quantitatively; and 3) in mice with intact Rhbg and Rhcg expression, metabolic acidosis does not induce maximal changes in PEPCK, NHE-3, and GS expression despite the presence of persistent metabolic acidosis.

Original languageEnglish
Pages (from-to)F789-F400
JournalAmerican Journal of Physiology - Renal Physiology
Volume306
Issue number4
DOIs
StatePublished - 15 Feb 2014

Keywords

  • Acid-base
  • Ammonia
  • Collecting duct

Fingerprint

Dive into the research topics of 'Effect of collecting duct-specific deletion of both Rh B glycoprotein (Rhbg) and Rh C glycoprotein (Rhcg) on renal response to metabolic acidosis'. Together they form a unique fingerprint.

Cite this