Rh B
glycoprotein (Rhbg) is a member of the Rh
glycoprotein family of
ammonia transporters. In the current study, we examine Rhbg's role in basal and
acidosis-stimulated
acid-base homeostasis.
Metabolic acidosis induced by HCl administration increased Rhbg expression in both the cortex and outer medulla. To test the functional significance of increased Rhbg expression, we used a Cre-loxP approach to generate mice with intercalated cell-specific Rhbg knockout (IC-Rhbg-KO). On normal diet, intercalated cell-specific Rhbg deletion did not alter urine
ammonia excretion, pH, or titratable
acid excretion significantly, but it did decrease
glutamine synthetase expression in the outer medulla significantly. After
metabolic acidosis was induced, urinary
ammonia excretion was significantly less in IC-Rhbg-KO than in control (C) mice on days 2-4 of
acid loading, but not on day 5. Urine pH and titratable
acid excretion and dietary
acid intake did not differ significantly between
acid-loaded IC-Rhcg-KO and C mice. In IC-Rhbg-KO mice,
acid loading increased connecting segment (CNT) cell and outer medullary collecting duct principal cell Rhbg expression. In both C and IC-Rhbg-KO mice,
acid loading decreased
glutamine synthetase in both the cortex and outer medulla; the decrease on day 3 was similar in IC-Rhbg-KO and C mice, but on day 5 it was significantly greater in IC-Rhbg-KO than in C mice. We conclude 1) intercalated cell Rhbg contributes to
acidosis-stimulated renal
ammonia excretion, 2) Rhbg in CNT and principal cells may contribute to renal
ammonia excretion, and 3) decreased
glutamine synthetase expression may enable normal rates of
ammonia excretion under both basal conditions and on day 5 of
acid loading in IC-Rhbg-KO mice.