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

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 HCO3(-) 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 phosphenolpyruvate 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.
AuthorsHyun-Wook Lee, Jill W Verlander, Mary E Handlogten, Ki-Hwan Han, I David Weiner
JournalAmerican journal of physiology. Renal physiology (Am J Physiol Renal Physiol) Vol. 306 Issue 4 Pg. F389-400 (Feb 15 2014) ISSN: 1522-1466 [Electronic] United States
PMID24338819 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, U.S. Gov't, Non-P.H.S.)
Chemical References
  • Cation Transport Proteins
  • Glycoproteins
  • Membrane Glycoproteins
  • Membrane Transport Proteins
  • RhBG protein, mouse
  • Rhcg protein, mouse
  • Slc9a3 protein, mouse
  • Sodium-Hydrogen Exchanger 3
  • Sodium-Hydrogen Exchangers
  • Ammonia
  • Phosphoenolpyruvate Carboxykinase (GTP)
  • Glutamate-Ammonia Ligase
Topics
  • Acidosis (genetics, metabolism)
  • Ammonia (metabolism)
  • Animals
  • Cation Transport Proteins (genetics, metabolism)
  • Glutamate-Ammonia Ligase (metabolism)
  • Glycoproteins (genetics, metabolism)
  • Kidney (metabolism)
  • Kidney Tubules, Collecting (metabolism)
  • Membrane Glycoproteins (genetics, metabolism)
  • Membrane Transport Proteins (genetics, metabolism)
  • Mice
  • Mice, Knockout
  • Phosphoenolpyruvate Carboxykinase (GTP) (metabolism)
  • Sodium-Hydrogen Exchanger 3
  • Sodium-Hydrogen Exchangers (metabolism)

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