Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P41181 (collecting duct)
 5,183 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:HCO-3 reabsorption in renal collecting duct of NHE-3-deficient mouse: a compensatory response. 1036 80