| First Author | Lee HW | Year | 2009 |
| Journal | Am J Physiol Renal Physiol | Volume | 296 |
| Issue | 6 | Pages | F1364-75 |
| PubMed ID | 19321595 | Mgi Jnum | J:196636 |
| Mgi Id | MGI:5488885 | Doi | 10.1152/ajprenal.90667.2008 |
| Citation | Lee HW, et al. (2009) Collecting duct-specific Rh C glycoprotein deletion alters basal and acidosis-stimulated renal ammonia excretion. Am J Physiol Renal Physiol 296(6):F1364-75 |
| abstractText | NH3 movement across plasma membranes has traditionally been ascribed to passive, lipid-phase diffusion. However, ammonia-specific transporters, Mep/Amt proteins, are present in primitive organisms and mammals express orthologs of Mep/Amt proteins, the Rh glycoproteins. These findings suggest that the mechanisms of NH3 movement in mammalian tissues should be reexamined. Rh C glycoprotein (Rhcg) is expressed in the collecting duct, where NH3 secretion is necessary for both basal and acidosis-stimulated ammonia transport. To determine whether the collecting duct secretes NH3 via Rhcg or via lipid-phase diffusion, we generated mice with collecting duct-specific Rhcg deletion (CD-KO). CD-KO mice had loxP sites flanking exons 5 and 9 of the Rhcg gene (Rhcg(fl/fl)) and expressed Cre-recombinase under control of the Ksp-cadherin promoter (Ksp-Cre). Control (C) mice were Rhcg(fl/fl) but Ksp-Cre negative. We confirmed kidney-specific genomic recombination using PCR analysis and collecting duct-specific Rhcg deletion using immunohistochemistry. Under basal conditions, urinary ammonia excretion was less in KO vs. C mice; urine pH was unchanged. After acid-loading for 7 days, CD-KO mice developed more severe metabolic acidosis than did C mice. Urinary ammonia excretion did not increase significantly on the first day of acidosis in CD-KO mice, despite an intact ability to increase urine acidification, whereas it increased significantly in C mice. On subsequent days, urinary ammonia excretion slowly increased in CD-KO mice, but was always significantly less than in C mice. We conclude that collecting duct Rhcg expression contributes to both basal and acidosis-stimulated renal ammonia excretion, indicating that collecting duct ammonia secretion is, at least in part, mediated by Rhcg and not solely by lipid diffusion. |
