title: HCO-3 reabsorption in renal collecting duct of NHE-3-deficient mouse: a compensatory response.
abstract: Mice with a targeted disruption of Na+/H+ exchanger NHE-3 gene show significant reduction in HCO-3 reabsorption in proximal tubule, consistent with the absence of NHE-3. Serum HCO-3, however, is only mildly decreased (P. Schulties, L. L. Clarke, P. Meneton, M. L. Miller, M. Soleimani, L. R. Gawenis, T. M. Riddle, J. J. Duffy, T. Doetschman, T. Wang, G. Giebisch, P. S. Aronson, J. N. Lorenz, and G. E. Shull. Nature Genet. 19: 282-285, 1998), indicating possible adaptive upregulation of HCO-3-absorbing transporters in collecting duct of NHE-3-deficient (NHE-3 -/-) mice. Cortical collecting duct (CCD) and outer medullary collecting duct (OMCD) were perfused, and total CO2 (net HCO-3 flux, JtCO2) was measured in the presence of 10 microM Schering 28080 (SCH, inhibitor of gastric H+-K+-ATPase) or 50 microM diethylestilbestrol (DES, inhibitor of H+-ATPase) in both mutant and wild-type (WT) animals. In CCD, JtCO2 increased in NHE-3 mutant mice (3.42 +/- 0.28 in WT to 5.71 +/- 0.39 pmol. min-1. mm tubule-1 in mutants, P < 0.001). The SCH-sensitive net HCO-3 flux remained unchanged, whereas the DES-sensitive HCO-3 flux increased in the CCD of NHE-3 mutant animals. In OMCD, JtCO2 increased in NHE-3 mutant mice (8.8 +/- 0.7 in WT to 14.2 +/- 0.6 pmol. min-1. mm tubule-1 in mutants, P < 0.001). Both the SCH-sensitive and the DES-sensitive HCO-3 fluxes increased in the OMCD of NHE-3 mutant animals. Northern hybridizations demonstrated enhanced expression of the basolateral Cl-/HCO-3 exchanger (AE-1) mRNA in the cortex. The gastric H+-K+-ATPase mRNA showed upregulation in the medulla but not the cortex of NHE-3 mutant mice. Our results indicate that HCO-3 reabsorption is enhanced in CCD and OMCD of NHE-3-deficient mice. In CCD, H+-ATPase, and in the OMCD, both H+-ATPase and gastric H+-K+-ATPase contribute to the enhanced compensatory HCO-3 reabsorption in NHE-3-deficient animals.
authors.affiliation: Department of Internal Medicine, Biochemistry and Microbiology, University of Cincinnati School of Medicine, Cincinnati, Ohio 45267, USA.
authors.forename: S
authors.initials: S
authors.lastname: Nakamura
authors.forename: H
authors.initials: H
authors.lastname: Amlal
authors.forename: P J
authors.initials: PJ
authors.lastname: Schultheis
authors.forename: J H
authors.initials: JH
authors.lastname: Galla
authors.forename: G E
authors.initials: GE
authors.lastname: Shull
authors.forename: M
authors.initials: M
authors.lastname: Soleimani
mesh_terms: D000042:Absorption; D000222:Adaptation, Physiological / Q000502:physiology; D000818:Animals; D017920:Antiporters / Q000235:genetics; D001639:Bicarbonates / Q000378:metabolism*; D027963:Chloride-Bicarbonate Antiporters; D004054:Diethylstilbestrol / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D007668:Kidney / Q000378:metabolism; D007672:Kidney Cortex; D007679:Kidney Medulla; D007685:Kidney Tubules, Collecting / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout / Q000235:genetics; D006180:Proton-Translocating ATPases / Q000037:antagonists & inhibitors / Q000187:drug effects; D012333:RNA, Messenger / Q000378:metabolism; D012016:Reference Values; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D013270:Stomach / Q000201:enzymology
chemical_list: D017920:Antiporters; D001639:Bicarbonates; D027963:Chloride-Bicarbonate Antiporters; D004791:Enzyme Inhibitors; D012333:RNA, Messenger; C000613386:Slc9a3 protein, mouse; D000074083:Sodium-Hydrogen Exchanger 3; D017923:Sodium-Hydrogen Exchangers; D004054:Diethylstilbestrol; D006180:Proton-Translocating ATPases