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.