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ABSORPTIVE FUNCTIONS OF THE NHE2 AND NHE3 SODIUM/PROTON EXCHANGERS IN INTESTINE AND KIDNEY

LEDOUSSAL, CLARA SIGISMONDI
http://rave.ohiolink.edu/etdc/view?acc_num=ucin990125141

Abstract Details

2001, PhD, University of Cincinnati, Medicine : Molecular Genetics, Biochemistry and Microbiology.
Maintenance of sodium-fluid volume homeostasis requires the tightly regulated activities of Na + /H + exchangers in intestine and kidney. Expression of NHE2 and NHE3 on intestinal and renal apical membranes suggests that both isoforms might contribute to sodium absorption. Studies with knockout mice showed that the loss of NHE3, but not NHE2, causes diarrhea, thereby demonstrating that NHE3 is the major absorptive exchanger and indicating that any remaining absorptive capacity contributed by NHE2 is not sufficient to compensate fully for the loss of NHE3. It remains possible, however, that NHE2 plays an important supplementary role in sodium absorption and blunts the severity of the diarrheal state in NHE3-deficient mice. To test this hypothesis in vivo , we crossed doubly heterozygous mice carrying null mutations in the Nhe2 and Nhe3 genes and assessed the diarrheal phenotype by analyzing the viability, systemic acid-base status, aldosterone levels, and intestinal contents of the resulting offspring. The loss of NHE2 in an NHE3-deficient background caused no apparent enhancement of the diarrheal state. To study the role of NHE2 and NHE3 in sodium-fluid volume homeostasis and renal sodium conservation, mice with Nhe2 and/or Nhe3 null mutations were fed a sodium-depleted diet, and urinary sodium excretion, blood pressure, and renal function were analyzed. Under Na + deprivation, Nhe2 null mice, on either a wild-type (Nhe2-/-Nhe3+/+) or an Nhe3 heterozygous background ( Nhe2 -/- Nhe3 +/- ), exhibited no increase in urinary sodium excretion and had similar blood pressure and glomerular filtration rate (GFR) relative to control mice ( Nhe2 +/+ Nhe3 +/+ , Nhe2 +/+ Nhe3 +/- , respectively), suggesting an absence of salt-wasting. In contrast, Nhe3 null mutants maintained on a sodium-depleted diet for three days exhibited hyponatremia, hyperkalemia, severe acidosis, mild urinary salt-wasting, and sharply reduced bodyweight, blood pressure and GFR. The overall study demonstrated a major role of NHE3 in intestinal and renal Na + reabsorption and maintenance of systemic electrolyte, acid-base, and fluid volume homeostasis, with little or no contribution from NHE2.
Dr. Gary E. Shull (Advisor)
1 p.
Biology, Animal Physiology
Na+/H+ exchanger; NHE2; NHE3; intestine; kidney

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Citations

  • LEDOUSSAL, C. S. (2001). ABSORPTIVE FUNCTIONS OF THE NHE2 AND NHE3 SODIUM/PROTON EXCHANGERS IN INTESTINE AND KIDNEY [Doctoral dissertation, University of Cincinnati]. OhioLINK Electronic Theses and Dissertations Center. http://rave.ohiolink.edu/etdc/view?acc_num=ucin990125141

    APA Style (7th edition)

  • LEDOUSSAL, CLARA. ABSORPTIVE FUNCTIONS OF THE NHE2 AND NHE3 SODIUM/PROTON EXCHANGERS IN INTESTINE AND KIDNEY. 2001. University of Cincinnati, Doctoral dissertation. OhioLINK Electronic Theses and Dissertations Center, http://rave.ohiolink.edu/etdc/view?acc_num=ucin990125141.

    MLA Style (8th edition)

  • LEDOUSSAL, CLARA. "ABSORPTIVE FUNCTIONS OF THE NHE2 AND NHE3 SODIUM/PROTON EXCHANGERS IN INTESTINE AND KIDNEY." Doctoral dissertation, University of Cincinnati, 2001. http://rave.ohiolink.edu/etdc/view?acc_num=ucin990125141

    Chicago Manual of Style (17th edition)

ucin990125141
© 2001, all rights reserved.
This open access ETD is published by University of Cincinnati and OhioLINK.